72 TRAIL-mediated apoptosis were somewhat distinct from those required for cell adhesion to CCN1. Collectively, these findings indicate that the ECM microenvironment, and in particular the presence or absence of CCN proteins, contribute to prostate carcinoma cell growth and survival, with the overall effect of the CCN proteins depending on the presence or absence of different extracellular ligands. These considerations emphasize on one hand the complexity of the action of CCN proteins, and on the other hand the difficulty of generating appropriate cell based assays to appropriately recapitulate the range of CCN- dependent activities that are observed in vivo. Moreover, these results are important for considering the overall anti- CCN therapies for disease, in that the overall vivo effect of CCN proteins at particular junctures of development, homeostasis and pathologies may differ widely. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. A. Leask References Babic AM, Kireeva ML, Kolesnikova TV, Lau LF (1998) CYR61, product of a growth factor-inducible immediate-early gene, promotes angiogenesis and tumor growth. Proc Natl Acad Sci USA 95:6355–6360 Franzen CA, Chen CC, Todorović V, Juric V, Monzon RI, Lau LF (2009) Matrix protein CCN1 is critical for prostate carcinoma cell prolifer- ation and TRAIL-induced apoptosis. Mol Cancer Res 7:1045–1055 Frazier K, Williams S, Kothapalli D, Klapper H, Grotendorst GR (1996) Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. J Invest Dermatol 107:404–411 Hishikawa K, Oemar BS, Tanner FC, Nakaki T, Lüscher TF, Fujii T (1999) Connective tissue growth factor induces apoptosis in human breast cancer cell line MCF-7. J Biol Chem 274:37461–37466 Lau LF, Lam SC (1999) The CCN family of angiogenic regulators: the integrin connection. Exp Cell Res 248:44–57 Leask A, Abraham DJ (2006) All in the CCN family: essential matricellular signaling modulators emerge from the bunker. J Cell Sci 119:4803–4810 Mo F-E, Lau LF (2006) The matricellular protein CCN1 is essential for cardiac development. Circ Res 99:961–969 Mo FE, Muntean AG, Chen CC, Stolz DB, Watkins SC, Lau LF (2002) CYR61 (CCN1) is essential for placental development and vascular integrity. Mol Cell Biol 22:8709–8720 Perbal B (2001) NOV (nephroblastoma overexpressed) and the CCN family of genes: structural and functional issues. Mol Pathol 54:57–79