Connective tissue growth factor as a major angiogenic agent that is induced by hypoxia in a human breast cancer cell line.
Connective tissue growth factor (CTGF) is known to be a potent angiogenic factor. Here, we present the evidence that the hypoxic induction of angiogenesis by human breast cancer cells (MDA-231) can be ascribed at least in part to CTGF. Our results indicate that (i) CTGF is abundantly present in MDA-231 cells in vitro and in vivo, (ii) its secretion is up-regulated by hypoxia, and (iii) its gene expression is enhanced in MDA-231 cells cultured under hypoxic conditions. These data suggest CTGF may stimulate angiogenesis by paracrine mechanisms, thereby contributing to the invasion of breast cancer cells. This is the first evidence that human cancer cells differentially express CTGF protein and mRNA under the control of hypoxic conditions.
Shimo
T
T
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, 700-8525, Okayama, Japan.
Kubota
S
S
Kondo
S
S
Nakanishi
T
T
Sasaki
A
A
Mese
H
H
Matsumura
T
T
Takigawa
M
M
D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D055513:Connective Tissue Growth Factor; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D016228:Endothelial Growth Factors; D006133:Growth Substances; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D055513:Connective Tissue Growth Factor