Inhibition of prostate tumor angiogenesis by the tumor suppressor CEACAM1.
We have previously shown that CEACAM1, a cell-adhesion molecule, acts as a tumor suppressor in prostate carcinoma. Expression of CEACAM1 in prostate cancer cells suppresses their growth in vivo. However, CEACAM1 has no effect on the growth of prostate cancer cells in vitro. This difference suggests that the antitumor effect of CEACAM1 may be due to inhibition of tumor angiogenesis, perhaps by increased secretion of antiangiogenic molecules from the cells. In this study, we have demonstrated that expression of CEACAM1 in DU145 prostate cancer cells induced the production of a factor or factors that specifically blocked the growth of endothelial but not epithelial cells. Conditioned medium from the CEACAM1-expressing cells but not control luciferase-expressing cells inhibited endothelial cell migration up a gradient of stimulatory vascular endothelial growth factor in vitro and inhibited corneal neovascularization induced by basic fibroblast growth factor in vivo. Moreover, conditioned medium from CEACAM1-expressing cells induced endothelial cell apoptosis in vitro. Only medium conditioned by CEACAM1 mutants that were able to suppress tumor growth in vivo could cause endothelial cell apoptosis. These observations suggest that CEACAM1-mediated tumor suppression in vivo is, at least in part, due to the ability of CEACAM1 to inhibit tumor angiogenesis.
Department of Microbiology-Immunology, R. H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Olga
O
Volpert
Weiping
W
Luo
Ta-Jen
TJ
Liu
Vicky T
VT
Estrera
Christopher
C
Logothetis
Sue-Hwa
SH
Lin
D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics; D015815:Cell Adhesion Molecules; D002455:Cell Division / Q000235:genetics; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned