Novel role of prostate-specific membrane antigen in suppressing prostate cancer invasiveness.
Novel role of prostate-specific membrane antigen in suppressing prostate cancer invasiveness.
复制标题
DOI：
10.1158/0008-5472.727.65.3
复制
发表时间：
2005-02
期刊：
影响因子：
11.2
通讯作者：
A. Ghosh;Xinning Wang;E. Klein;W. Heston
中科院分区：
文献类型：
--
作者：
A. Ghosh;Xinning Wang;E. Klein;W. Heston
前列腺特异性膜抗原（PSMA）是一种II型跨膜糖蛋白，在前列腺癌中过表达。PSMA是一种独特的细胞表面标志物，受雄激素负调控，广泛用于激素难治性癌和转移灶的成像。PSMA是一种羧肽酶，具有两种重要的酶功能，即叶酸水解酶和NAALAD酶。PSMA还表现出内吞功能，其中它通过内吞囊泡自发地释放。PSMA在前列腺癌的各个阶段过表达，包括雄激素敏感性和非依赖性疾病，在治疗后早期复发时表达增加。我们已经使用体外侵袭试验来探索PSMA在前列腺癌细胞转移中的可能作用。内源性表达PSMA的雄激素依赖性前列腺癌细胞系（例如，LNCaP、MDA PCa2b和CWR22Rv1）与雄激素非依赖性PC 3或DU 145细胞相比侵袭性更小，这两种细胞都不表达PSMA。PSMA在PC3细胞中的异位表达降低了这些细胞的侵袭性，表明表达PSMA的细胞的侵袭能力的这种降低是由于PSMA表达而不是不同前列腺癌细胞系的内在特性。此外，PSMA表达的敲低使LNCaP细胞的侵袭性增加5倍。最后，缺乏羧肽酶活性的PSMA突变体的表达降低了PSMA表达对侵袭性的影响。因此，似乎酶活性与PSMA对侵袭性的影响有关。
Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein, is overexpressed in prostate cancer. PSMA is a unique cell surface marker, negatively regulated by androgen and extensively used for imaging of hormone refractory carcinomas and metastatic foci. PSMA is a carboxypeptidase with two important enzymatic functions, namely, folate hydrolase and NAALADase. PSMA also exhibits an endocytic function, in which it spontaneously recycles through endocytic vesicles. PSMA is overexpressed at various stages of prostate cancer, including androgen-sensitive and -independent disease, increased in expression with early relapse after therapy. We have used in vitro invasion assays to explore the possible role of PSMA in the metastasis of prostate cancer cells. Androgen-dependent prostate cancer lines, which express PSMA endogenously (e.g., LNCaP, MDA PCa2b, and CWR22Rv1) are less invasive compared with androgen-independent PC3 or DU145 cells, neither of which expresses PSMA. Ectopic expression of PSMA in PC3 cells reduced the invasiveness of these cells, suggesting that this reduction in the invasion capability of PSMA-expressing cells is due to PSMA expression and not to intrinsic properties of different prostate cancer cell lines. Furthermore, knockdown of PSMA expression increased invasiveness of LNCaP cells by 5-fold. Finally, expression of PSMA mutants lacking carboxypeptidase activity reduced the impact of PSMA expression on invasiveness. Thus, it seems that the enzymatic activity is associated with the effect of PSMA on invasiveness.