Perbal A, Perbal B. CCN proteins, microenvironment, communication and signaling: why did we need a new journal? J Cell Commun Signal. 2007 Jun;1(1):1-3. doi: 10.1007/s12079-007-0007-x. Epub 2007 May 25. No abstract available.
Organization of International Conferences
International Workshop on Retroviral Pathogenesis 1996, 2005, Saint-Malo, France
International Workshop on the CCN family of Genes Organizer,2000, 2002, 2004, Saint-Malo, France Co-Organiser, 2006, Okayama, Japan Co-Organiser, 2008, Toronto, Canada Co-Organiser, 2010, Newcastle, Ireland Organiser, 2013, Nice, France Organiser, 2015, Nice, France Organiser, 2017, Saint-Malo, France Co-Organiser, 2019, Niagara Falls, Canada Organiser, 2022, Nice, France
I created the Laboratory of Molecular and Viral Oncology “Laboratoire d’Oncologie Virale et Moléculaire” in 1982. This laboratory was hosted successively at the “Institut Curie”, the “Hôpital Saint-Antoine (INSERM)”, and the “Université Paris 7 D. Diderot . Over the past 26 years, the research which was performed in the Laboratoire d’Oncologie Virale et Moléculaire has been funded by l’ Association pour la Recherche contre le Cancer (ARC), La Fondation pour la Recherche Médicale (FRM), La ligue Nationale contre le Cancer (LNCC, Comités de Paris, du Cher et de l’Indre), l’ Association Française contre les myopathies (AFM), La Fédération nationale des Groupements des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC), Le Centre National de la Recherche Scientifique (CNRS), L’Institut Curie, L’institut National de la Santé et de la Recherche Médicale (INSERM), Le Ministère de l’Education Nationale de la Recherche et de la Technologie (MENRT), l’Université Paris 7 D.Diderot, The European Union, and private donations.
Our studies were aimed at understanding :
the molecular basis for the Myeloblastosis Associated Virus (MAV) tumorigenic potential
the biochemical properties, mode of action and biological role of the CCN3 (NOV) protein in normal and pathological conditions with a particular emphasis to the potential use of the CCN3 protein as a new tool for molecular medicine
The MAV strains usually induce osteopetrosis, lymphomas, and nephroblastomas in chicken (Perbal, Infect Agents Dis., 1995). Molecular cloning of a MAV strain inducing specifically nephroblastoma when injected in day-old chicken (Perbal, 1985, Soret et al. 1985) allowed to establish that MAV-induced nephroblastoma represent a unique animal model for the Wilms’s tumor (Perbal Crit Rev Oncog., 1994). The identification of the MAV integration sites allowed us to identify several genes whose viral induced alteration is associated to cancer development (Li et al. 2006). Although early studies identified ccn3 as an integration site for MAV (Joliot et al. 1992) and suggested that it might be localized in a genomic hot spot for MAV integration, more recent results indicated that MAV did not integrate frequently in the vicinity of ccn3 (Li et al. 2006).
Studies performed in the laboratory (Perbal B. Mol Pathol. 2001, Perbal 2006) showed that the CCN3 protein may be acting either as a positive or negative regulator of cell growth in normal conditions. Disregulation of the ccn3 gene expression and abnormal production, processing or localization of the CCN3 protein is associated to malignancy in several tumor cases. Studies that we have performed established that CCN3 detection in tumor samples is associated to a favorable outcome in several types of tumors. In other cases, expression of ccn3 is associated to metastatic potentiality of the tumor cells (Planque and Perbal, Cancer Cell Int. 2003, Perbal, Expert Rev Mol Diagn. 2003). The value of CCN3 as a prognostic marker has been established in the case of osteosarcomas (Perbal et al. 2008) and melanomas (Vallacchi et al. 2008). The level of circulating CCN3 protein is also being used as a marker of pathological condition in several cases. Methods allowing quantitation of CCN3 in biological fluids and its use as a tool for molecular medicine are being developed. We have already established that the expression of ccn3 is reducing the tumorigenic potential of glioblastomas, choriocarcinomas, Ewing’s tumors and melanomas. These observations set the stage for developing protocols for genetic therapy of these tumors.
Studies performed in the laboratory also aimed at identifying the proteins and ligands which interact with CCN3 and allow it to play its regulatory role in the control of cell attachement, spreading, proliferation and differentiation. Purification of the CCN3 protein has allowed us to undertake structural and functional studies which have already permitted the identification of signaling pathways into which CCN3 is acting.
Over the past few years, after we had identified biologically active truncated CCN3 proteins with different subcellular localization (Perbal 2004, Planque et al. 2006), several laboratories also reported the existence of truncated and rearranged forms of other CCN proteins (Perbal et al. 2023). Since the nuclear CCN3 proteins detected in cancer cells have been shown to regulate transcription, we have proposed a model in which a balanced production of secreted CCN3 protein with anti-proliferative activity and nuclear CCN3 protein with pro-proliferative and oncogenic activities is required for the control of normal proliferation and differentiation. Disruption of this balance is associated to cancer development.
Selected Publications in the field of cell communication and signaling
Cooperation is the key: the CCN biological system as a gate to high complex protein superfamilies’ signaling. J Cell Commun Signal. 2023 In press
Another Step Forward to the understanding of Biological Signaling Networks. J Cell Commun Signal. 2022 Sep;16(3):311-312
Perbal B, Gabaron S.
Mastering health: liberating beauty : Will the cosmetics of tomorrow be genetic? JCell Commun Signal. 2021 Dec;15(4):483-490.
JCCS editorial board: a wide array of expertise. J Cell Commun Signal. 2020 Mar;14(1):5-17
CCN proteins are part of a multilayer complex system: a working model. J Cell Commun Signal. 2019 Dec;13(4):437-439
Perbal B, Tweedie S, Bruford E.
The official unified nomenclature adopted by the HGNC calls for the use of the acronyms, CCN1-6, and discontinuation in the use of CYR61, CTGF, NOV and WISP 1-3 respectively. J Cell Commun Signal. 2018 Dec;12(4):625-629
Yeger H, Brigstock D, Fisher G, Lau L, Leask A, Perbal B. Report on the 9th international workshop on the CCN family of genes, November 2-7, 2017, Saint-Malo, France. J Cell Commun Signal. 2018 Sep;12(3):505-511.
Perbal B. The concept of the CCN protein family revisited: a centralized coordination network. J Cell Commun Signal. 2018 Mar;12(1):3-12.
Perbal B. Once upon a time …A special issue for the 10th anniversary of the Journal of Cell Communication and Signaling. J Cell Commun Signal. 2018 Mar;12(1):1-2. doi: 10.1007/s12079-018-0460-8. Epub 2018 Feb 12.
Dombrowski Y, O’Hagan T, Dittmer M, Penalva R, Mayoral SR, Bankhead P, Fleville S, Eleftheriadis G, Zhao C, Naughton M, Hassan R, Moffat J, Falconer J, Boyd A, Hamilton P, Allen IV, Kissenpfennig A, Moynagh PN, Evergren E, Perbal B, Williams AC, Ingram RJ, Chan JR, Franklin RJM, Fitzgerald DC. Regulatory T cells promote myelin regeneration in the central nervous system. Nat Neurosci. 2017 May;20(5):674-680.
Perbal B. Neuroscience and psychological studies sustain the cognitive benefits of print reading. J Cell Commun Signal. 2017 Mar;11(1):1-4.
Fong KW, Zhao JC, Kim J, Li S, Yang YA, Song B, Rittie L, Hu M, Yang X, Perbal B, Yu J. Polycomb-Mediated Disruption of an Androgen Receptor Feedback Loop Drives Castration-Resistant Prostate Cancer. Cancer Res. 2017 Jan 15;77(2):412-422.
Perbal A, Perbal B. The CCN family of proteins: a 25th anniversary picture. J Cell Commun Signal. 2016 Sep;10(3):177-190
Yeger H, Perbal B. CCN family of proteins: critical modulators of the tumor cell microenvironment. J Cell Commun Signal. 2016 Sep;10(3):229-240.
Perbal A, Perbal B. The CCN family of proteins: a 25th anniversary picture. J Cell Commun Signal. 2016 Sep;10(3):177-190. Epub 2016 Aug 31.
Zhang C, van der Voort D, Shi H, Zhang R, Qing Y, Hiraoka S, Takemoto M, Yokote K, Moxon JV, Norman P, Rittié L, Kuivaniemi H, Atkins GB, Gerson SL, Shi GP, Golledge J, Dong N, Perbal B, Prosdocimo DA, Lin Z. Matricellular protein CCN3 mitigates abdominal aortic aneurysm. J Clin Invest. 2016 May 2;126(5):2012.
Perbal B, Lau L, Lyons K, Kubota S, Yeger H, Fisher G. Report on the 8th international workshop on the CCN family of genes – Nice November 3-8, 2015. J Cell Commun Signal. 2016 Mar;10(1):77-86.
Perbal B Tests génétiques en accès libre : Danger ou opportunité ? Le petit juriste Juillet-Août 2015
Perbal B Pour une liberté surveillée des tests génétiques Petites affiches Lextenso 8-9 Septembre 2015 N° 179-180
Perbal B. What kind of a life for a scientific journal? J Cell Commun Signal. 2015 Sep;9(3):201-6.
Perbal B Communication is the key. : Part 2 : Direct to consumer genetics in our future daily life ? J Cell Commun Signal. 2014 Dec;8(4):275-8
Paradis R, Lazar N, Antinozzi P, Perbal B, Buteau J. Nov/Ccn3, a novel transcritional target to FoxO1, impairs pancreatic beta-cell function. PLoS One 2013 May;8(5):e64957.
Perbal B CCN Proteins : A Centralized Communication System. J Cell Commun Signal. 2013 Aug;7(3):169-77.
Abd El Kader T, Kubota S, Janune D, Nishida T, Hattori T, Aoyama E, Perbal B, Kuboki T, Takigawa M. Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family. J Cell Commun Signal. 2013 Aug;7(1):11-8.
van Roeyen CR, Boor P, Borkham-Kamphorst E, Rong S, Kunter U, Martin IV, Kaitovic A, Fleckenstein S, Perbal B, Trautwein C, Weiskirchen R, Ostendorf T, Floege J. A novel, dual role of CCN3 in experimental glomerulonephritis: pro-angiogenic and antimesangioproliferative effects. Am J Pathol. 2012 May;180(5):1979-90.
Perbal B CCN3: the-pain-killer inside me. J Cell Commun Signal. 2012 Jun;6(2):117-20. Epub 2012 Mar 30.
Janune D, Kubota S, Nishida T, Kawaki H, Perbal B, Iida S, Takigawa M. Novel effects of CCN3 that may direct the differentiation of chondrocytes. FEBS Lett. 2011 Aug 23. [Epub ahead of print]
McCallum L, Lu W, Price S, Lazar N, Perbal B, Irvine AE. CCN3 suppresses mitogenic signalling and reinstates growth control mechanisms in Chronic Myeloid Leukaemia. J Cell Commun Signal. 2011 Jul 20. [Epub ahead of print]
Kawaki H, Kubota S, Suzuki A, Suzuki M, Kohsaka K, Hoshi K, Fujii T, Lazar N, Ohgawara T, Maeda T, Perbal B, Takano-Yamamoto T, Takigawa M. Differential roles of CCN family proteins during osteoblast differentiation: Involvement of Smad and MAPK signaling pathways. Bone. 2011 Jul 7. [Epub ahead of print]
Suresh S, McCallum L, Lu W, Lazar N, Perbal B, Irvine AE. MicroRNAs 130a/b are regulated by BCR-ABL and downregulate expression of CCN3 in CML. J Cell Commun Signal. 2011 Aug;5(3):183-91. Epub 2011 Jun 3.
Ouellet V, Tiedemann K, Mourskaia A, Fong JE, Tran-Thanh D, Amir E, Clemons M, Perbal B, Komarova SV, Siegel P. CCN3 impairs osteoblast and stimulates osteoclast differentiation to favor breast cancer metastasis to bone Am J Pathol 2011 May;178(5):2377-88
Rittié L,Perbal B,Castellot JJ, Orringer JS, Voorhees JJ, Fisher GJ Spatial-temporal modulation of CCN proteins during wound healing in human skin in vivo J Cell Commun Signal. 2011 in press DOI: 10.1007/s12079-010-0114-y
Lin Z, Natesan V, Shi H, Hamik A, Kawanami D, Hao C, Mahabaleshwar GH, Wang W, Jin ZG, Atkins GB, Firth SM, Rittié L, Perbal B, Jain MK. A novel role of CCN3 in regulating endothelial inflammation. J Cell Commun Signal. 2010 Oct;4(3):141-53. Epub 2010 Aug 11.PMID:
Riser BL, Najmabadi F, Perbal B, Rambow JA, Riser ML, Sukowski E, Yeger H, Riser SC, Peterson DR. CCN3/CCN2 regulation and the fibrosis of diabetic renal disease. J Cell Commun Signal. 2010 Mar;4(1):39-50. Epub 2010 Feb 9.PMID: 20195391
Lemaire R, Farina G, Bayle J, Dimarzio M, Pendergrass SA, Milano A, Perbal B, Whitfield ML, Lafyatis R. Antagonistic effect of the matricellular signaling protein CCN3 on TGF-beta- and Wnt-mediated fibrillinogenesis in systemic sclerosis and Marfan syndrome. J Invest Dermatol. 2010 Jun;130(6):1514-23. Epub 2010 Feb 25. Erratum in: J Invest Dermatol. 2010 Oct;130(10):2517. Perbal, Bernard [added]. PMID: 20182440
Shimoyama T, Hiraoka S, Takemoto M, Koshizaka M, Tokuyama H, Tokuyama T, Watanabe A, Fujimoto M, Kawamura H, Sato S, Tsurutani Y, Saito Y, Perbal B, Koseki H, Yokote K. CCN3 inhibits neointimal hyperplasia through modulation of smooth muscle cell growth and migration. Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):675-82.
Pasmant E, Ortonne N, Rittié L, Laurendeau I, Lévy P, Lazar V, Parfait B, Leroy K, Dessen P, Valeyrie-Allanore L, Perbal B, Wolkenstein P, Vidaud M, Vidaud D, Bièche I. Differential expression of CCN1/CYR61, CCN3/NOV, CCN4/WISP1, and CCN5/WISP2 in neurofibromatosis type 1 tumorigenesis. J Neuropathol Exp Neurol. 2010 Jan;69(1):60-9.
Sin WC, Tse M, Planque N, Perbal B, Lampe PD, Naus CC. Matricellular protein CCN3 (NOV) regulates actin cytoskeleton reorganization. J Biol Chem. 2009 Oct 23;284(43):29935-44. Epub 2009 Aug 25.
Perbal B, Lazar N, Zambelli D, Lopez-Guerrero JA, Llombart-Bosch A, Scotlandi K, Picci P. Prognostic relevance of CCN3 in Ewing sarcoma. Hum Pathol. 2009 Oct;40(10):1479-86. Epub 2009 Aug 19.
Tong Z, Chen R, Alt DS, Kemper S, Perbal B, Brigstock DR. Susceptibility to liver fibrosis in mice expressing a connective tissue growth factor transgene in hepatocytes. Hepatology. 2009 Sep;50(3):939-47.
McCallum L, Lu W, Price S, Lazar N, Perbal B, Irvine AE. CCN3: a key growth regulator in Chronic Myeloid Leukaemia. J Cell Commun Signal. 2009 Jun;3(2):115-24. Epub 2009 Jul 22.
Perbal B. Alternative splicing of CCN mRNAs …. it has been upon us. J Cell Commun Signal. 2009 Jun;3(2):153-7. Epub 2009 Apr 28.
Riser BL, Najmabadi F, Perbal B, Peterson DR, Rambow JA, Riser ML, Sukowski E, Yeger H, Riser SC. CCN3 (NOV) is a negative regulator of CCN2 (CTGF) and a novel endogenous inhibitor of the fibrotic pathway in an in vitro model of renal disease. Am J Pathol. 2009 May;174(5):1725-34. Epub 2009 Apr 9.
Irvine AE, Perbal B, Yeger H. Report on the fifth international workshop on the CCN family of genes. J Cell Commun Signal. 2008 Dec;2(3-4):95-100. Epub 2009 Jan 21.
Holbourn KP, Acharya KR, Perbal B. The CCN family of proteins: structure-function relationships. Trends Biochem Sci. 2008 Oct;33(10):461-73. Epub 2008 Sep 11.
Perbal B. CCN3: Doctor Jekyll and Mister Hyde. J Cell Commun Signal. 2008 Jun;2(1-2):3-7. Epub 2008 Sep 12.
Rittié L, Perbal B. Enzymes used in molecular biology: a useful guide. J Cell Commun Signal. 2008 Jun;2(1-2):25-45. Epub 2008 Sep 3
Kawaki H, Kubota S, Suzuki A, Lazar N, Yamada T, Matsumura T, Ohgawara T, Maeda T, Perbal B, Lyons KM, Takigawa M. Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage. J Bone Miner Res. 2008 Nov;23(11):1751-64.
Yeger H, Perbal B. The CCN family of genes: a perspective on CCN biology and therapeutic potential. J Cell Commun Signal. 2008 Jun 21. [Epub ahead of print]
Perbal B. Avian Myeoloblastosis Virus (AMV) : only one side of the coin. Retrovirology. 2008 Jun 16;5(1):49. [Epub ahead of print]
Perbal B. CCN3-mutant mice are distinct from CCN3-null mice. J Cell Commun Signal 2007 Dec;1(3-4):229-30
Kawaki H , Kubota S, Suzuki A, Lazar N, Yamada T, Matsumura T, Ohgawara T, Maeda T, Perbal B, Lyons K, Takigawa M. Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 revealed by a comprehensive analysis of the CCN family proteins in cartilage J. Bone Miner. Res. 2008 ;
Perbal B, Zuntini M, Zambelli D, Serra M, Sciandra M, Cantiani L, Lucarelli E, Picci P, Scotlandi K. Prognostic value of CCN3 in osteosarcoma. Clin Cancer Res. 2008 Feb 1;14(3):701-9.
Vallacchi V, Daniotti M, Ratti F, Di Stasi D, Deho P, De Filippo A, Tragni G, Balsari A, Carbone A, Rivoltini L, Parmiani G, Lazar N, Perbal B, Rodolfo M. CCN3/nephroblastoma overexpressed matricellular protein regulates integrin expression, adhesion, and dissemination in melanoma. Cancer Res. 2008 Feb 1;68(3):715-23. Erratum in: Cancer Res. 2008 Mar 15;68(6):2051.
Subramaniam MM, Lazar N, Navarro S, Perbal B, Llombart-Bosch A. Expression of CCN3 protein in human Wilms’ tumors: immunohistochemical detection of CCN3 variants using domain-specific antibodies. Virchows Arch. 2008 Jan;452(1):33-9. Epub 2007 Dec 8.
Perbal A, Perbal B. CCN proteins, microenvironment, communication and signaling: why did we need a new journal? J Cell Commun Signal. 2007 Jun;1(1):1-3. Epub 2007 May 25.
Lazar N, Manara C, Navarro S, Bleau A-M, Llombart-Bosch A, Scotlandi K, Planque N, Perbal B. Domain-specific CCN3 antibodies as unique tools for structural and functional studies J. Cell Commun Signal. 2007 Sep;1(2):91-102. Epub 2007 Sep 8.
Fukunaga-Kalabis M, Martinez G, Telson SM, Liu ZJ, Balint K, Juhasz I, Elder DE, Perbal B, Herlyn M. Downregulation of CCN3 expression as a potential mechanism for melanoma progression. Oncogene. 2008 Apr 17;27(18):2552-60. Epub 2007 Oct 29.
van Roeyen CR, Eitner F, Scholl T, Boor P, Kunter U, Planque N, Grone HJ, Bleau AM, Perbal B, Ostendorf T, Floege J. CCN3 is a novel endogenous PDGF-regulated inhibitor of glomerular cell proliferation. Kidney Int. 2007 Oct 3; [Epub ahead of print]
Bleau AM, Planque N, Lazar N, Zambelli D, Ori A, Quan T, Fisher G, Scotlandi K, Perbal B. Antiproliferative activity of CCN3: Involvement of the C-terminal module and post-translational regulation. J Cell Biochem. 2007 Mar 5; [Epub ahead of print]
Minamizato T, Sakamoto K, Liu T, Kokubo H, Katsube KI, Perbal B, Nakamura S, Yamaguchi A. CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways. Biochem Biophys Res Commun. 2007 Mar 9;354(2):567-573. Epub 2007 Jan 16.
Perbal B. The CCN3 protein and cancer. Adv Exp Med Biol. 2006;587:23-40. Review.
Fukunaga-Kalabis M, Martinez G, Liu ZJ, Kalabis J, Mrass P, Weninger W, Firth SM, Planque N, Perbal B, Herlyn M. CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1. J Cell Biol. 2006 Nov 20;175(4):563-9. Epub 2006 Nov 13.
Yan X, Baxter RC, Perbal B, Firth SM. The aminoterminal insulin-like growth factor (IGF) binding domain of IGF binding protein-3 cannot be functionally substituted by the structurally homologous domain of CCN3. Endocrinology. 2006 Nov;147(11):5268-74. Epub 2006 Aug 24.
Perbal B. New insight into CCN3 interactions – Nuclear CCN3 : fact or fantasy? Cell Commun Signal. 2006 Aug 8;4:6.
McCallum L, Price S, Planque N, Perbal B, Pierce A, Whetton AD, Irvine AE. A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation. Blood. 2006 Sep 1;108(5):1716-23. Epub 2006 May 2.
Planque N, Long Li C, Saule S, Bleau AM, Perbal B. Nuclear addressing provides a clue for the transforming activity of amino-truncated CCN3 proteins. J Cell Biochem. 2006 Sep 1;99(1):105-16.
Perbal B. NOV story: the way to CCN3. Cell Commun Signal. 2006 Feb 20;4:3.
Li CL, Coullin P, Bernheim A, Joliot V, Auffray C, Zoroob R, Perbal B. Integration of Myeloblastosis Associated Virus proviral sequences occurs in the vicinity of genes encoding signaling proteins and regulators of cell proliferation. Cell Commun Signal. 2006 Jan 10;4:1.
Benini S, Perbal B, Zambelli D, Colombo MP, Manara MC, Serra M, Parenza M, Martinez V, Picci P, Scotlandi K. In Ewing’s sarcoma CCN3(NOV) inhibits proliferation while promoting migration and invasion of the same cell type. Oncogene. 2005 Jun 23;24(27):4349-61.
Bleau AM, Planque N, Perbal B. CCN proteins and cancer: two to tango. Front Biosci. 2005 May 1;10:998-1009.
Kyurkchiev S, Yeger H, Bleau AM, Perbal B. Potential cellular conformations of the CCN3(NOV) protein. Cell Commun Signal. 2004 Sep 10;2(1):9.
Fu CT, Bechberger JF, Ozog MA, Perbal B, Naus CC. CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible mechanism of connexin-mediated growth suppression. J Biol Chem. 2004 Aug 27;279(35):36943-50. Epub 2004 Jun 21.
Gellhaus A, Dong X, Propson S, Maass K, Klein-Hitpass L, Kibschull M, Traub O, Willecke K, Perbal B, Lye SJ, Winterhager E. Connexin43 interacts with NOV: a possible mechanism for negative regulation of cell growth in choriocarcinoma cells. J Biol Chem. 2004 Aug 27;279(35):36931-42. Epub 2004 Jun 4.
Katsube K, Chuai ML, Liu YC, Kabasawa Y, Takagi M, Perbal B, Sakamoto K. The expression of chicken NOV, a member of the CCN gene family, in early stage development. Brain Res Gene Expr Patterns. 2001 Aug;1(1):61-5.
Yu C, Le AT, Yeger H, Perbal B, Alman BA. NOV (CCN3) regulation in the growth plate and CCN family member expression in cartilage neoplasia. J Pathol. 2003 Dec;201(4):609-15.
Perbal B. Communication is the key. Cell Commun Signal. 2003 Oct 27;1(1):3.
Lombet A, Planque N, Bleau AM, Li CL, Perbal B. CCN3 and calcium signaling. Cell Commun Signal. 2003 Aug 15;1(1):1.
Perbal B. The CCN3 (NOV) cell growth regulator: a new tool for molecular medicine. Expert Rev Mol Diagn. 2003 Sep;3(5):597-604.
Planque N, Perbal B. A structural approach to the role of CCN (CYR61/CTGF/NOV) proteins in tumourigenesis. Cancer Cell Int. 2003 Aug 22;3(1):15.
Brigstock DR, Goldschmeding R, Katsube KI, Lam SC, Lau LF, Lyons K, Naus C, Perbal B, Riser B, Takigawa M, Yeger H. Proposal for a unified CCN nomenclature. Mol Pathol. 2003 Apr;56(2):127-8.
Perbal B, Brigstock DR, Lau LF. Report on the second international workshop on the CCN family of genes. Mol Pathol. 2003 Apr;56(2):80-5.
Coullin P, Li CL, Ziercher L, Auffray C, Bernheim A, Zoorob R, Perbal B. Assignment of the chicken NOV gene (alias CCN3) to chromosome 2q34–>q36: Conserved and compared synteny between avian, mouse and human. Cytogenet Genome Res. 2002;97(1-2):140C.
Li CL, Martinez V, He B, Lombet A, Perbal B. A role for CCN3 (NOV) in calcium signalling. Mol Pathol. 2002 Aug;55(4):250-61.
Sakamoto K, Yamaguchi S, Ando R, Miyawaki A, Kabasawa Y, Takagi M, Li CL, Perbal B, Katsube K. The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway. J Biol Chem. 2002 Aug 16;277(33):29399-405. Epub 2002 Jun 05.
Manara MC, Perbal B, Benini S, Strammiello R, Cerisano V, Perdichizzi S, Serra M, Astolfi A, Bertoni F, Alami J, Yeger H, Picci P, Scotlandi K. The expression of ccn3(nov) gene in musculoskeletal tumors. Am J Pathol. 2002 Mar;160(3):849-59.
Perbal B. Les protéines CCN : quand multimodulaire rime avec multifonctionnel. Médecine-Sciences. 2002 Jun;18 :745-56
Thomopoulos GN, Kyurkchiev S, Perbal B. Immunocytochemical localization of NOVH protein and ultrastructural characteristics of NCI-H295R cells. J Submicrosc Cytol Pathol. 2001 Jul;33(3):251-60.
Glukhova L, Angevin E, Lavialle C, Cadot B, Terrier-Lacombe MJ, Perbal B, Bernheim A, Goguel AF. Patterns of specific genomic alterations associated with poor prognosis in high-grade renal cell carcinomas. Cancer Genet Cytogenet. 2001 Oct 15;130(2):105-10.
Gupta N, Wang H, McLeod TL, Naus CC, Kyurkchiev S, Advani S, Yu J, Perbal B, Weichselbaum RR. Inhibition of glioma cell growth and tumorigenic potential by CCN3 (NOV). Mol Pathol. 2001 Oct;54(5):293-9.
Maillard M, Cadot B, Ball RY, Sethia K, Edwards DR, Perbal B, Tatoud R. Differential expression of the ccn3 (nov) proto-oncogene in human prostate cell lines and tissues Mol Pathol. 2001 Aug;54(4):275-80
Su BY, Cai WQ, Zhang CG, Martinez V, Lombet A, Perbal B. The expression of ccn3 (nov) RNA and protein in the rat central nervous system is developmentally regulated Mol Pathol 2001 Jun;54(3):184-91.
Perbal B. NOV (nephroblastoma overexpressed) and the CCN family of genes: structural and functional issues. Mol Pathol. 2001 Apr;54(2):57-79. doi: 10.1136/mp.54.2.57
2016 : A year for JCCS Editorial changes and CCN3 KO mice at ICCNS
At the dawn of 2016, it is my great pleasure to wish all our readers an excellent new year, full of familial satisfaction and professional success.
The year 2016 will be an important one for the Journal of Cell Communication and Signaling as it will be assigned its first official impact factor (IF) through the indexing of its contents by Thomson Reuter.
Earning of the IF is a major step in the life of a scientific journal as I had discussed in a previous editorial (Perbal, 2015).
It also coicindes with the recent merger of Springer Science + Business Media and part of Macmillan Science and Education (including the nature Publishing Group). As a result of this merger, responsibility for the Journal of Cell Communication has been transferred from Thijs van Vlijmen to Meran Owen. Thijs had been assigned JCCS seven years ago, shortly after Peter Butler and I had agreed to create JCCS as the continuation of the former Cell Communication and Signaling that I had created at BMC. During these past seven years, Thijs supported our commitment and efforts to improve the scientific quality and audience of the journal.
Meran Owen holds a Ph.D. in Genetics and spent many years as a researcher in Canada and in the United Kingdom. Meran worked with Elsevier as an Editor of Trends in Biotechnology, part of the Business Development group and as Senior Publishing Editor in Biomedicine/Life Sciences Division at Springer for 9 years. We trust that Meran Owen’s qualifications and his past experience in publishing are assets that should prove very precious for the scientific future of JCCS.
Let me take this opportunity to express my sincerest thanks to those who shared with me the responsibility of bringing JCCS to the attention of the scientific community as an essential journal in the field of cell communication and signaling, in spite of the very tough competition from other major publishing groups who all created journals on the same topic after our initial creation of CCS
Bucket list for 2016
In addition to increasing the net number of articles submitted to the main sections of JCCS (Pathology and Translational Research, Molecular Signaling and Reviews), our goals for 2016 also include an increase in communications submitted either as Bits and Bytes or commentaries.
Although our section editors spend quite a significant amount of time to convince colleagues to submit comments it seems that these sections do not attract many authors, even though they are also indexed on PubMed as original manuscripts as soon as they are accepted.
This section could be much more lively, as an open forum, with comments presented by senior and young researchers on any field of interest. These could then trigger discussions and exchange of viewpoints about new trends, techniques, or scientific progress.
Getting people to commit themselves to editing a special issue of JCCS on a topic of their choice would fullfil another wish that we would like to see come true in 2016. <br /> Solicited thematic issues can cover any field of interest for the CCN and signaling scientific communities. Information on these can be obtained by contacting me directly.
The 8th International Workhop on the CCN family of genes
In addition to regular research manuscripts and reviews, this first issue of 2016 also contains a report on the 8th International Workshop on the CCN family which was held from November 3_8 in Nice and includes the abstracts of the talks that were presented. The meeting was a resounding success voiced by all who attended. We were honored to host two special guests.
Judith Campisi received the 2015 ICCNS Springer award for her achievements in the field of cancer research and senescence. Robert Baxter, a previous ICCNS-Springer Awardee, presented a special conference on IGFBP3 and cancer.
We are very grateful to both of these talented colleagues for staying during the whole time of the meeting, thereby providing a unique opportunity to all those who wanted to meet them and discuss various aspects in their presentations.
Everyone agreed that the quality of the presentations given at the meeting is attaining a very high standard and is greatly contributing to the scientific recognition of the CCN field and one that is very productive. The place and dates of the next meeting will be announced in these pages and on the ICCNS web site
ICCNS Scientific Board
The Scientific Board of the International CCN Society has been renewed this year, as the mandate of M. Takigawa ended in 2015. Lester Lau accepted my invitation to become the President of the Scientific Board in addition to his present position as head of the ICCNS Council.
In an effort to reinforce and create productive contacts for the ICCNS with other societies with whom we share scientific interest, a few colleagues have accepted our invitation to become the « liaison » with other societies, in order to foster dynamic exchanges and work on possible participations in each other’s meetings. The new composition of the ICCNS advisory scientific board will be published shortly on the ICCNS web site.
In conclusion, we expect 2016 to be a banner year for progress and the exchange of new ideas and valuable reagents. Along this line I have worked out a special agreement with the Japanese colleagues with whom I published on the isolation and partial study of the only true CCN3 knockout mouse model available as of today (Shimoyama et al. 2010, Leask 2010). The ICCNS is now allowed to provide the CCN3 KO mice to all ICCNS members who will request them. Details regarding the procedure will be published on the ICCNS website shortly. We do hope that this first step in providing access to a certified reagent will signal the beginning of a wider sharing of reagents, something we had proposed several years ago with J. Castellot on the ICCNS web site, and a goal discussed at each International Workshop over many years.
Paul Bornstein is currently Emeritus Professor of Biochemistry and Medicine at the University of Washington. He received his BA from Cornell University and MD from New York University. He trained in Surgery and Internal Medicine at Yale New Haven Hospital, and then spent a year as an Arthritis Foundation Postdoctoral Fellow at the Pasteur Institute in Paris.
In 1963, Dr. Bornstein joined the US Public Health Service as a Research Investigator and worked for four years on collagen biochemistry with Karl Piez at the National Institutes of Health. He was discharged from the USPHS in 1967 as a Senior Surgeon, with a rank of Commander in the US Coast Guard.
After leaving NIH, Dr Bornstein accepted a position as Assistant Professor of Medicine at the University of Washington, and in the following year obtained a joint appointment in Biochemistry. In 1973 he achieved the rank of full professor in Biochemistry and Medicine Over the years, Dr Bornstein’s research interests have changed from protein chemistry to the cell biology of cell-matrix interactions, and then to the molecular biology of thrombospondins and other matricellular proteins. He has held positions as Visiting Professor at UCSD, with Jonathan Singer, at Louis Pasteur University in Strasbourg with Pierre Chambon, and at the Whitehead Institute, MIT, with Rudolph Jaenisch.
Dr. Bornstein has been awarded a Lederle Medical Faculty Award, a Research Career Development Award from the NIH, a Josiah Macy Faculty Scholar Award, a John Simon Guggenheim Memorial Fellowship, a MERIT Award from the NIH, and most recently a Solomon Berson Alumni Achievement Award in Basic Science from NYU School of Medicine. He has been elected to membership in the American Society for Clinical Investigation and in the Association for American Physicians. He has also served on many Editorial Boards including the American Journal for Cell Biology, and the Journal of Biological Chemistry.
Dr. Bornstein founded the American Society for Matrix Biology in 2000 and served as its second Vice-President and President; he also served as Vice-President and President of the International Society for Matrix Biology, chaired two Gordon Conferences in the matrix field, and served on numerous Academic and Industrial Advisory Boards He is the author of nearly 300 research papers, reviews and book chapters.
Edward J. Calabrese is a Professor of Toxicology at the University of Massachusetts, School of Public Health and Health Sciences, Amherst. Dr. Calabrese has researched extensively in the area of host factors affecting susceptibility to pollutants, and is the author of over 600 papers in scholarly journals, as well as more than 10 books, including Principles of Animal Extrapolation; Nutrition and Environmental Health, Vols. I and II; Ecogenetics; Multiple Chemical Interactions; Air Toxics and Risk Assessment; and Biological Effects of Low Level Exposures to Chemicals and Radiation. Along with Mark Mattson (NIH) he is a co-editor of the recently published book entitled: Hormesis: A Revolution in Biology, Toxicology and Medicine.
Dr. Calabrese has been a member of the U.S. National Academy of Sciences and NATO Countries Safe Drinking Water committees, and on the Board of Scientific Counselors for the Agency for Toxic Substances and Disease Registry (ATSDR). Dr. Calabrese also serves as Chairman of the Biological Effects of Low Level Exposures (BELLE) and as Director of the Northeast Regional Environmental Public Health Center at the University of Massachusetts. Dr. Calabrese was awarded the 2009 Marie Curie Prize for his body of work on hormesis.
Over the past 20 years Professor Calabrese has redirected his research to understanding the nature of the dose response in the low dose zone and underlying adaptive explanatory mechanisms. Of particular note is that this research has led to important discoveries which indicate that the most fundamental dose response in toxicology and pharmacology is the hormetic-biphasic dose response relationship. These observations are leading to a major transformation in improving drug discovery, development, and in the efficiency of the clinical trial, as well as the scientific foundations for risk assessment and environmental regulation for radiation and chemicals.
After 18 years as Director of the Kolling Institute of Medical Research at the University of Sydney, Rob Baxter stepped down in January 2012 to continue his research on the biochemistry, cell biology, and endocrinology of the insulin-like growth factors and their binding proteins. He remains at the Kolling Institute where he heads the Hormones and Cancer Division.
His research has contributed to understanding both the regulation of normal tissue and body growth, and the aberrant cellular growth in cancer and overgrowth syndromes. His group’s achievements include characterizing the protein complexes that carry IGFs in the circulation, and discovering how IGF binding proteins affect cancer cell growth by modulating cell signaling pathways. His collaborative clinical studies have significantly advanced understanding of the role of these proteins in a variety of conditions including pregnancy, tumor-related hypoglycemia, and critical illness. He also heads the laboratory for Cellular and Diagnostic Proteomics in the Kolling Institute, and is involved in biomarker discovery studies in breast and pancreatic cancers, and growth disorders.
Rob received his PhD in Biochemistry from the University of Sydney in 1973, was awarded a DSc in 1990, and was elected a Fellow of the Australian Academy of Science in 2004. He has over 300 research publications, cited >18,000 times. He has served on journal Editorial Boards including Endocrinology, American Journal of Physiology (Endo & Metabolism), and Journal of Biological Chemistry. He has given keynote plenary lectures at conferences in Australia, Europe, South America and the USA, and has received several major research awards including the Dale Medal (Society for Endocrinology, UK), Wellcome Australia Medal, Lemberg Medal (ASBMB) and Ramaciotti Medal for Excellence in Biomedical Research. He served as president of the Endocrine Society of Australia from 1988-1990, chaired the National Committee for Biomedical Sciences of the Australian Academy of Science from 2006-2009, and is currently Vice-President of the International Society for IGF Research.
Carlo M. Croce, MD, is the Professor and Chair of Molecular Virology, Immunology and Medical Genetics, Director of the Human Cancer Genetics Program, and Director of the Institute of Genetics at The Ohio State University Comprehensive Cancer Center. His research has revealed the variety of mutated genes involved in leukemias, lymphomas and other cancers.
Dr. Croce is world-renowned for his contributions involving the genes and genetic mechanisms implicated in the pathogenesis of human cancer. During the course of his career, he discovered the juxtaposition of the human immunoglobulin genes to the MYC oncogene, the deregulation of MYC in Burkitt lymphoma, the ALL1 gene involved in acute leukemias, the TCL1 gene associated with T-cell leukemias, and cloned and characterized the BCL2 gene involved in follicular lymphoma.
Dr. Croce has also uncovered the early events involved in the pathogenesis of lung, nasopharyngeal, head and neck, esophageal, gastrointestinal and breast cancers. His discoveries have led to revolutionary innovations in the development of novel and successful approaches to cancer prevention, diagnosis, monitoring and treatment, based on gene-target discovery, verification and rational drug development.
He is a member of the National Academy of Sciences, Institute of Medicine, American Academy of Arts and Sciences and an AAAS Fellow. He is principal investigator on seven federal research grants and has more than 1000 peer-reviewed, published research papers.
Judith Campisi received a PhD in Biochemistry from the State University of New York at Stony Brook, and postdoctoral training in cell cycle regulation and cancer at the Dana-Farber Cancer Institute and Harvard Medical School.
As an Assistant Professor at the Boston University Medical School, she began studying the role of cellular senescence in suppressing the development cancer. However, she soon became convinced that senescent cells also contributed to aging. She left Boston University as an Associate Professor to accept a Senior Scientist position at the Lawrence Berkeley National Laboratory in 1991. In 2002, she established a laboratory at the Buck Institute for Age Research, where she is a Professor.
At both institutions, Judith Campisi established a broad program to understand various aspects of aging, with an emphasis on the interface between cancer and aging. Her laboratory made several pioneering discoveries in these areas, and her research continues to challenge and alter existing paradigms.
In recognition of the quality of her research and leadership, Judith Campisi has received numerous awards. These include two MERIT awards from the US National Institute on Aging, awards from the AlliedSignal Corporation, Gerontological Society of America and American Federation for Aging Research, the Longevity prize from the international IPSEN Foundation, the Bennett Cohen award from the University of Michigan and the Schober award from Halle University (Germany).
Judith Campisi is an elected a fellow of the American Association for the Advancement of Science, and serves on numerous national and international editorial and scientific advisory boards.
On the occasion of the ICCNS-Springer Award, Professor Campisi will give a presentation entitled :
Cancer and aging: Rival demons and signaling mechanisms
SYNOPSIS: Aging is the single largest risk factor for developing a panoply of diseases, including diseases as diverse as neurodegeneration and cancer. I will discuss recent progress in the common signaling mechanisms and cell fate responses that drive disparate age-related diseases. At the heart of this convergence is the cell fate decision termed cellular senescence. The pleiotropic senescence response entails a complex signaling cascade that ultimately determines important physiological responses ranging from tumor suppression to wound healing.
Dr. Meenhard Herlyn is Caspar Wistar Professor for Melanoma Research and Director of the Melanoma Research Center at The Wistar Institute in Philadelphia, as well as Founding President of the Society for Melanoma Research. Born and educated in Germany, Dr. Herlyn received his D.V.M. at the University of Veterinary Medicine, Hanover in 1970 and went on to receive a D.Sc. in medical microbiology at the University of Munich in 1976. That same year he came to The Wistar Institute as an associate scientist, where he worked in the emerging field of monoclonal antibodies, a technology that formed the basis of a portion of today’s new targeted therapeutics.
In 1981, Dr. Herlyn became an assistant professor and established a laboratory that is, today, one the largest and best-known research groups on the study of melanoma biology. Current major efforts include the ability to model the microenvironment of normal and diseased human tissue through 3-D artificial skin, providing his laboratory with a unique insight into cancer research. His laboratory also seeks to further define the various signaling pathways that work in cancer cells in order to discover new opportunities to inhibit cancer growth through targeted therapeutics. Since therapy is increasingly guided by the genetic aberrations in tumors, Dr. Herlyn and colleagues are developing combinations of compounds that take into account the genetic signature of tumors, with the specific goal of individualized cancer therapy.
Another major effort of his laboratory is the study of therapy resistance and tumor dormancy. Tumor cells can become dormant in primary tumors or at any time after metastatic dissemination and can persist in the dormant state for many years, allowing tumors to resist treatment. Dr. Herlyn’s working hypothesis is that defined tumor subpopulations are central to dormancy and drug resistance due to their slow turnover and their non-responsiveness to growth signals. His efforts seek to define how tumor cells escape dormancy for growth, invasion, and metastasis, and how to best develop strategies for therapy. Because of the significance of immunotherapy in treatment of melanoma patients, the laboratory has developed two models that closely mimic the conditions in humans with the ultimate goal of combining targeted and immune therapies.
Dr. Herlyn has over 500 peer-reviewed publications, over 85% of which are on melanoma. He has presented at dozens of national and international congresses and meetings, and has received accolades from prestigious organizations such as the Melanoma Research Foundation, American Skin Association, American Cancer Society, Society for Melanoma Research and more. He serves on numerous national and international editorial and scientific advisory boards.
On the occasion of the ICCNS-Springer Award, Dr. Herlyn will give a presentation entitled:
Understanding the biology of stem cells and melanocytes to develop new strategies for melanoma therapy
SYNOPSIS:We have developed a series of in vitro and in vivo models to elucidate the functions of genes associated with normal skin homeostasis and melanoma progression and metastasis formation. Using cDNA and RNA interference constructs and libraries in viral vectors, we have investigated the crosstalk of genes associated with cell-cell and cell-matrix interactions, intracellular signaling and transcriptional regulation. Three-dimensional skin with a ‘dermis’ containing fibroblasts and neural crest-like stem cells and ‘epidermis’ of keratinocytes and melanocytes mimic the skin environment, which we begin to populate also with inflammatory and immune cells. The 3-D models allow us to investigate mechanisms of transformation for melanocytes and stem cells, which are obtained from patients with high susceptibility for melanoma.
Work on tumor subpopulations lead to the development of a dynamic model of tumor maintenance, in which cells remained quiescence for prolonged periods of time until signals from the microenvironment activate them for proliferation. Invasion may occur even during dormancy, a cellular state of high resistance to any conventional therapy. The laboratory has been active in the development of targeted therapies in melanoma using small molecule inhibitors specific for kinases in key signaling pathways for proliferation and survival and of target genes that play critical roles in melanocyte development and tumor invasion and metastasis. We are developing groups of melanomas amendable to therapy with combinations of three or more drugs to also kill those cells that survive even double agent therapies.
Major emphasis is on intrinsic (innate) and acquired resistance in melanoma, in which cells escape primary therapy but can be successfully eliminated with inhibitors that are specifically targeting subpopulations of cells. Signaling inhibitors are also combined with immunotherapeutics using for the in vivo studies mice humanized with CD34+ hematopoietic stem cells from cord blood or induced pluripotent (iPS) cells and HLA-matched or autologous patient-derived xenografts (PDX), respectively. Thus, our work spans basic biological to translational investigations with defined clinical outcome. Strong emphasis is placed on multi-disciplinary collaborations with intra- and inter-institutional research groups.