title: CCN3: Doctor Jekyll and Mister Hyde.
abstract: CCN proteins are key regulators of signaling pathways that are essential for the control of normal life, from birth to death. As such, they make use of their unique mosaic structure to interact with several other regulatory proteins and ligands that control the fate of living cells. The various functions attributed to the CCN proteins may sometimes appear contradictory, but this situation reflects the complexity of the multimolecular scaffolds in which CCN proteins are engaged and the critical impact of the microenvironment that dictates the bioavailability of the elementary building blocks. CCN3 is one of the best examples of a CCN protein showing biological properties which may at first glance appear opposite or contradictory. Indeed, CCN3 acts both as a tumor suppressor and is associated with higher metastatic potential. Furthermore, the physical interaction of CCN3 with VEGF and its potential antiangionenic activity in glioma cells are in apparent contradiction with its proangiogenic activity in rabbit cornea. In this communication, I am revisiting the observations that led us to these apparent contradictions. After pointing out how the methodologies that were employed might have contributed to the confusion, I briefly discuss the dual biological activities of CCN3 in the context of tumor cell engineering and survival prognosis.
authors.affiliation: Research and Development - L'Oréal USA, 111 Terminal Avenue, Clark, NJ, 07066, USA, bperbal@gmail.com.
authors.forename: Bernard
authors.initials: B
authors.lastname: Perbal
references.citation: Lancet. 2004 Jan 3;363(9402):62-4
references.pmid: 14723997
references.citation: Mol Pathol. 2001 Oct;54(5):293-9
references.pmid: 11577170
references.citation: J Cell Sci. 2006 Dec 1;119(Pt 23):4803-10
references.pmid: 17130294
references.citation: Cell Commun Signal. 2006 Feb 20;4:3
references.pmid: 16504021
references.citation: Blood. 2006 Sep 1;108(5):1716-23
references.pmid: 16670264
references.citation: Gene. 1999 Oct 1;238(2):471-8
references.pmid: 10570975
references.citation: Cancer Res. 2008 Feb 1;68(3):715-23
references.pmid: 18245471
references.citation: Am J Pathol. 1998 Jun;152(6):1563-75
references.pmid: 9626060
references.citation: Clin Cancer Res. 2008 Feb 1;14(3):701-9
references.pmid: 18245529
references.citation: Mol Pathol. 2001 Apr;54(2):57-79
references.pmid: 11322167
references.citation: Crit Rev Oncog. 1994;5(6):589-613
references.pmid: 8519812
references.citation: J Cell Biol. 2006 Nov 20;175(4):563-9
references.pmid: 17101694
references.citation: Mol Pathol. 2001 Aug;54(4):275-80
references.pmid: 11477145
references.citation: Oncogene. 2005 Jun 23;24(27):4349-61
references.pmid: 15824736
references.citation: Biochem Biophys Res Commun. 2008 Apr 11;368(3):808-14
references.pmid: 18275847
references.citation: Mol Cell Biol. 1992 Jan;12(1):10-21
references.pmid: 1309586
references.citation: J Biol Chem. 2003 Jun 27;278(26):24200-8
references.pmid: 12695522
references.citation: Mol Pathol. 1999 Apr;52(2):84-91
references.pmid: 10474687
references.citation: J Cell Biochem. 2006 Sep 1;99(1):105-16
references.pmid: 16598765
references.citation: Cancer Genet Cytogenet. 2001 Oct 15;130(2):105-10
references.pmid: 11675130
references.citation: J Cell Biochem. 2007 Aug 15;101(6):1475-91
references.pmid: 17340618
references.citation: Am J Pathol. 2002 Mar;160(3):849-59
references.pmid: 11891184
references.citation: Cell Commun Signal. 2006 Aug 08;4:6
references.pmid: 16895594
references.citation: Trends Biochem Sci. 2008 Oct;33(10):461-73
references.pmid: 18789696