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CCN1 and CCN2: blood brothers in angiogenic action

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Journal of Cell Communication and Signaling Aims and scope

Abstract

CCN2/connective tissue growth factor (CTGF) is a matricellular protein essential for skeletal development during embryogenesis. In adulthood, aberrant CCN2 expression is associated with many malignancies and fibrosis of virtually every organ. Despite its prominent expression in endothelial cells in the vasculature, the role of CCN2 in vessel development was unknown. In a recent study, Hall-Glenn et al. (PLoS ONE 7:e30562) have revealed the role of CCN2 in developmental angiogenesis through a detailed analysis of how CCN2 mediates the interaction between vascular endothelial cells and pericytes. In addition, CCN2 also regulates endothelial basement membrane formation during vessel formation. Here I compare the angiogenic activities of CCN2 during embryogenesis to those of its homologous family member CCN1 (CYR61), which is essential for cardiovascular development. Understanding the angiogenic actions of CCN1 and CCN2 may have implication in the development of therapeutic strategies targeting these proteins for the treatment of diseases such as cancer and fibrosis.

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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 U S A 95:6355–6360

    Article  PubMed  CAS  Google Scholar 

  • Babic AM, Chen C-C, Lau LF (1999) Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin αvβ3, promotes endothelial cell survival, and induces angiogenesis in vivo. Mol Cell Biol 19:2958–2966

    PubMed  CAS  Google Scholar 

  • Chen C-C, Mo F-E, Lau LF (2001) The angiogenic inducer Cyr61 induces a genetic program for wound healing in human skin fibroblasts. J Biol Chem 276:47329–47337

    Article  PubMed  CAS  Google Scholar 

  • Hall-Glenn F, De Young RA, Huang BL, van Handel B, Hofmann JJ, Chen TT, Choi A, Ong JR, Benya PD, Mikkola H, Iruela-Arispe ML, Lyons KM (2012) CCN2/connective tissue growth factor is essential for pericyte adhesion and endothelial basement membrane formation during angiogenesis. PLoS ONE 7:e30562

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto G, Inoki I, Fujii Y, Aoki T, Ikeda E, Okada Y (2002) Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165. J Biol Chem 277:36288–36295

    Article  PubMed  CAS  Google Scholar 

  • Inoki I, Shiomi T, Hashimoto G, Enomoto H, Nakamura H, Makino K, Ikeda E, Takata S, Kobayashi K, Okada Y (2002) Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis. FASEB J 16:219–221

    PubMed  CAS  Google Scholar 

  • Ivkovic S, Yoon BS, Popoff SN, Safadi FF, Libuda DE, Stephenson RC, Daluiski A, Lyons KM (2003) Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development 130:2779–2791

    Article  PubMed  CAS  Google Scholar 

  • Jeansson M, Gawlik A, Anderson G, Li C, Kerjaschki D, Henkelman M, Quaggin SE (2011) Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Invest 121:2278–2289

    Article  PubMed  CAS  Google Scholar 

  • Jun JI, Lau LF (2011) Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov 10:945–963

    Article  PubMed  CAS  Google Scholar 

  • Leu S-J, Lam SCT, Lau LF (2002) Proangiogenic activities of CYR61 (CCN1) mediated through integrins αvβ3 and α6β1 in human umbilical vein endothelial cells. J Biol Chem 277:46248–46255

    Article  PubMed  CAS  Google Scholar 

  • Lin CG, Leu SJ, Chen N, Tebeau CM, Lin SX, Yeung CY, Lau LF (2003) CCN3 (NOV) is a novel angiogenic regulator of the CCN protein family. J Biol Chem 278:24200–24208

    Article  PubMed  CAS  Google Scholar 

  • Lindahl P, Johansson BR, Leveen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245

    Article  PubMed  CAS  Google Scholar 

  • Mason RM (2009) Connective tissue growth factor(CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it? J Cell Commun Signal 3:95–104

    Article  PubMed  Google Scholar 

  • Mo F-E, Lau LF (2006) The matricellular protein CCN1 is essential for cardiac development. Circ Res 99:961–969

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Perbal B (2008) CCN3: doctor jekyll and mister hyde. J Cell Commun Signal 2:3–7

    Article  PubMed  Google Scholar 

  • Shimo T, Nakanishi T, Nishida T, Asano M, Kanyama M, Kuboki T, Tamatani T, Tezuka K, Takemura M, Matsumura T, Takigawa M (1999) Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo. J Biochem (Tokyo) 126:137–145

    Article  CAS  Google Scholar 

  • Yang F, Tuxhorn JA, Ressler SJ, McAlhany SJ, Dang TD, Rowley DR (2005) Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis. Cancer Res 65:8887–8895

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago College of Medicine, 900 South Ashland Avenue, Chicago, IL, 60607-7170, USA

    Lester F. Lau

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  1. Lester F. Lau
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Correspondence to Lester F. Lau.

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Lau, L.F. CCN1 and CCN2: blood brothers in angiogenic action. J. Cell Commun. Signal. 6, 121–123 (2012). https://doi.org/10.1007/s12079-012-0169-z

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  • DOI: https://doi.org/10.1007/s12079-012-0169-z

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