Metastasis suppressor CC3 inhibits angiogenic properties of tumor cells in vitro.
Resistance to apoptosis and ability to promote angiogenesis are integral features of the metastatic phenotype. Human gene CC3 is a metastasis suppressor for variant small cell lung carcinoma and a mouse melanoma in vivo. We have shown previously that metastasis-suppressing function of CC3 might be due at least in part to the ability of CC3 protein to predispose tumor cells to apoptosis. Here we demonstrate that CC3 has a previously unidentified effect on the ability of tumor cells to induce angiogenesis in vitro. Expression of CC3 in three different tumor cell lines significantly diminished their angiogenic character as manifested in the in vitro proliferation and migration assays with endothelial cells of both macro- and microvascular origin. Expression of CC3 induced changes in RNA levels of several angiogenic modulators consistent with the overall reduction in angiogenic properties. These results indicate that expression of CC3 has a dual effect on phenotype of tumor cells ultimately inhibiting their metastatic potential.
NicAmhlaoibh
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R
Cancer Research Institute, University of California San Francisco, 94143-0128, USA.
Shtivelman
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E
D000123:Acetyltransferases; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D008175:Lung Neoplasms / Q000473:pathology*; D008222:Lymphokines / Q000235:genetics; D009389:Neovascularization, Pathologic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D008222:Lymphokines; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D000123:Acetyltransferases; C111246:HTATIP2 protein, human