Association of prostate-specific membrane antigen with caveolin-1 and its caveolae-dependent internalization in microvascular endothelial cells: Implications for targeting to tumor vasculature

被引:23
作者
Anilkumar, Gopalakrishnapillai
Barwe, Sonali P.
Chnistiansen, Jason J.
Rajasekaran, Sigrid A.
Kohn, Donald B.
Rajasekaran, Ayyappan K.
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[2] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90095 USA
关键词
prostate cancer; prostate-specific membrane antigen; human microvascular endothelial cells; neovasculature; endocytosis; caveolae;
D O I
10.1016/j.mvr.2006.03.004
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Prostate-specific membrane antigen (PSMA) is a transmembrane protein with a highly restricted profile of expression. Expression is primarily limited to secretory cells of the prostatic epithelium, with elevated levels observed in prostate cancer. As an integral membrane protein correlated with prostate cancer, PSMA offers a potentially valuable target for immunotherapy. PSMA is also detected in the neovasculature of a variety of solid tumors but not in the endothelial cells of preexisting blood vessels. Although the significance of PSMA expression in these cells remains elusive, this pattern of expression implies that PSMA may perform a functional role in angiogenesis and may offer a therapeutic target for the treatment of a broad spectrum of solid tumors. In this study, we have expressed PSMA in human microvascular endothelial cells and demonstrate that PSMA binds to caveolin-1 and undergoes internalization via a caveolae-dependent mechanism. The association between PSMA and caveolae in endothelial cells may provide important insight into PSMA function and ways to best exploit this protein for therapeutic benefit. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:54 / 61
页数:8
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