Involvement of CTGF, a hypertrophic chondrocyte-specific gene product, in tumor angiogenesis.
Connective tissue growth factor (CTGF) is a potent secreted signaling factor which functions in multiple stages of angiogenesis. In the present study, we examined the role of CTGF in tumor angiogenesis and made the following observations: (1) Histological analysis of human breast cancer (MDA231) cell and human fibrosarcoma (HT1080) cell xenografts in BALB/c nude mice showed a high level of neovascularization. Human squamous cell carcinoma (A431) xenografts induced only a low level of neovascularization. (2) CTGF mRNA was strongly expressed in MDA231 and in HT1080 cells in vivo and in vitro, but not in A431 cells. (3) CTGF protein was markedly produced in MDA231 cells and HT1080 cells and secreted into culture medium, and its production was greater during phases of growth rather than confluency. (4) Production of CTGF in bovine aorta endothelial cells was induced by CTGF, VEGF, bFGF and TGF-beta. (5) Neovascularization induced by HT1080 cells or MDA231 cells on chicken chorioallantoic membrane was suppressed in the presence of neutralizing CTGF-specific polyclonal antibody. These results suggest that CTGF regulates progression in tumor angiogenesis and the release or secretion of CTGF from tumor cells is essential for the angiogenesis.
Shimo
T
T
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Nakanishi
T
T
Nishida
T
T
Asano
M
M
Sasaki
A
A
Kanyama
M
M
Kuboki
T
T
Matsumura
T
T
Takigawa
M
M
D000482:Allantois; D000818:Animals; D001011:Aorta; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D002417:Cattle; D002645:Chickens; D002823:Chorion; D055513:Connective Tissue Growth Factor; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005354:Fibrosarcoma / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000032:analysis / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D016228:Endothelial Growth Factors; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D055513:Connective Tissue Growth Factor