CEA-related cell adhesion molecule-1 is involved in angiogenic switch in prostate cancer
2006
We demonstrate here that epithelial
carcinoembryonic antigen(CEA)-related cell adhesion molecule-1 (CEA-CAM1) downregulation in prostate
intraepithelial neoplasia(PIN) is inversely correlated with its upregulation in adjacent
blood vessels. CEACAM1 silencing in prostate cancer cell line DU-145 via small interfering ribonucleic acid (siRNA) increased but its overexpression suppressed the expression of angiogenic/lymphangiogenic factors such as vascular endothelial growth factor (VEGF)-A, - C and -D, and angiogenic inhibitor collagen 18/
endostatin. Furthermore, CEACAM1 overexpression in DU-145 cells increased but CEACAM1 silencing reduced
angiopoietin-1 expression. Inverse relation was found for
angiopoietin-2. Supernatant of CEACAMl-overexpressing DU-145 suppressed but that of CEACAM1-silenced increased the VEGF-induced endothelial tubes. Electron microscopically the majority of PIN-associated
blood vesselswas structurally destabilized exhibiting endothelial
fenestration, trans- and inter-endothelial gaps. In some PIN areas, invasion of single tumor cells into the destabilized
blood vesselswas observed. These data show that disappearance of epithelial CEACAM1 in PIN is accompanied by its upregulation in adjacent vasculature which apparently correlates with vascular destabilization and increased vascularization of prostate cancer. Strategies to either conserve the epithelial CEACAM1 or to target endothelial CEACAM1 might be useful for an anti-angiogenic therapy of prostate cancer.
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