Moderate expression of prostate-specific membrane antigen, a tissue differentiation antigen and folate hydrolase, facilitates prostate carcinogenesis.
Moderate expression of prostate-specific membrane antigen, a tissue differentiation antigen and folate hydrolase, facilitates prostate carcinogenesis.
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DOI：
10.1158/0008-5472.can-08-2328
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发表时间：
2008-11-01
期刊：
影响因子：
11.2
通讯作者：
Bacich DJ
中科院分区：
文献类型：
--
作者：
Yao V;Parwani A;Maier C;Heston WD;Bacich DJ
PSMA是一种具有叶酸水解酶活性的分化抗原，其表达增加是前列腺癌进展的独立标志。在前列腺中表达中等水平的人PSMA的小鼠在9个月后会出现PIN样病变。这项研究的目的是确定PSMA是否与前列腺癌的发生和发展有关；如果是，PSMA可能发挥其作用的可能机制。利用PSMA转基因小鼠的前列腺，我们建立了一种组织重组模型，该模型显示了具有腺癌特征的小的非典型腺体。在由野生型兄弟姐妹的前列腺组织组成的组织重组中没有观察到这一点。来自PSMA转基因组织重组体的细胞能够在半固体琼脂中形成集落。PSMA可能通过增加细胞的侵袭能力来促进这种表型。在体外侵袭实验中，PC-3细胞异位表达PSMA可增加细胞的侵袭能力，这一作用可被叶酸所竞争。这些结果表明PSMA促进了前列腺癌的发展，这些细胞的侵袭能力可能受到叶酸水平的调节。这些发现表明了一种新的机制，可能有助于叶酸在癌症预防中的已知作用，并可能导致PSMA抑制剂作为前列腺癌的新型化学预防药物的使用。此外，我们的模型应该被证明是有用的，进一步解剖与前列腺癌发生和发展有关的途径。
Increased expression of PSMA, a differentiation antigen with folate hydrolase activity, is an independent marker of prostate cancer progression. Mice expressing moderate levels of human PSMA in their prostate develop PIN-like lesions by 9 months. The aim of this study was to determine whether PSMA is involved in prostate carcinogenesis and progression; and if so the possible mechanism by which PSMA may exert its effects. Utilizing prostates from PSMA-transgenic mice, we developed a tissue recombinant model which exhibits small atypical glands with features of adenocarcinoma. This was not observed in tissue recombinants that were composed of prostate tissues from the wild-type siblings. Cells from PSMA-transgenic tissue recombinants have the ability to form colonies in semi-solid agar. PSMA may facilitate this phenotype by increasing the cells’ invasive ability. Ectopic PSMA expression on PC-3 cells increased cells’ invasive capacity in in vitro invasion assays, which could be competed out by folic acid. These results suggest PSMA facilitates the development of prostate cancer, and the invasive ability of these cells may be modulated by folate levels. These findings demonstrate a novel mechanism that may contribute to the known role of folate in cancer prevention, and may lead to the use of PSMA inhibitors as novel chemopreventive agents for prostate cancer. Moreover, our model should prove useful for further dissecting pathways involved in prostate carcinogenesis and progression.