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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Inhibition of prostate tumor angiogenesis by the tumor suppressor CEACAM1
Olga Volpert1, Weiping Luo, Ta-Jen Liu
1Department of Microbiology-Immunology, R. H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Abstract:
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.
Insights
Carcinoma cell adhesion molecule CEACAM1 suppresses tumor growth by inhibiting angiogenesis. CEACAM1 expression in prostate cancer cells promotes the secretion of factors that block blood vessel formation and induce cancer cell death.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Carcinoma cell adhesion molecule CEACAM1 previously identified as a tumor suppressor in prostate cancer.
- CEACAM1 expression inhibits prostate cancer cell growth in vivo but not in vitro, suggesting a role in anti-angiogenesis.
Purpose of the Study:
- To investigate the mechanism by which CEACAM1 suppresses tumor growth, specifically its effect on angiogenesis.
- To determine if CEACAM1 induces the production of anti-angiogenic factors.
Main Methods:
- Expression of CEACAM1 in DU145 prostate cancer cells.
- Analysis of conditioned medium from CEACAM1-expressing cells for effects on endothelial and epithelial cells in vitro.
- Assessment of conditioned medium's effect on corneal neovascularization in vivo.
- Evaluation of endothelial cell apoptosis induction by conditioned medium.
Main Results:
- Conditioned medium from CEACAM1-expressing cells inhibited endothelial cell growth, migration, and induced apoptosis.
- CEACAM1 expression blocked endothelial cell migration towards vascular endothelial growth factor.
- CEACAM1 inhibited basic fibroblast growth factor-induced corneal neovascularization in vivo.
- Only CEACAM1 mutants suppressing tumor growth in vivo induced endothelial cell apoptosis.
Conclusions:
- CEACAM1-mediated tumor suppression in prostate carcinoma is partly due to the inhibition of tumor angiogenesis.
- CEACAM1 promotes the secretion of factors that specifically target endothelial cells, inhibiting neovascularization and inducing apoptosis.
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