The androgen-regulated type II serine protease TMPRSS2 is differentially expressed and mislocalized in prostate adenocarcinoma
The androgen-regulated type II serine protease TMPRSS2 is differentially expressed and mislocalized in prostate adenocarcinoma
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DOI：
10.1002/path.2330
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发表时间：
2008-06-01
影响因子：
7.3
通讯作者：
Nelson, P. S.
中科院分区：
文献类型：
--
作者：
Lucas, J. M.;True, L.;Nelson, P. S.
跨膜丝氨酸蛋白酶 2 (TMPRSS2) 是二型跨膜蛋白酶 (TTSP) 家族的雄激素调节成员。 TTSP 家族的另外两个成员，matriptase 和 hepsin，在前列腺腺癌中过度表达，并从机制上影响癌细胞的侵袭和转移。本研究旨在确定原发性和转移性前列腺癌中 TMPRSS2 蛋白的表达。我们开发了一种能够灵敏、特异检测 TMPRSS2 蛋白的单克隆抗体。测量了雄激素对 TMPRSS2 的调节以及精液中的存在情况。通过免疫组织化学评估了 415 例原发性前列腺癌和 144 例前列腺癌转移病例中的 TMPRSS2 定位和表达。我们确定 TMPRSS2 蛋白表达受雄激素调节，并且 TMPRSS2 是正常精液蛋白质组的组成部分。 TMPRSS2蛋白在前列腺中大量表达，在结肠、胃、附睾和乳腺的上皮细胞中表达水平较低。胰腺腺泡、肝胆管、睾丸 Leydig 细胞和肾脏也表达 TMPRSS2。在前列腺中，TMPRSS2 蛋白特异性定位于分泌上皮，在朝向导管腔的质膜中表达增强。与正常上皮相比，肿瘤性前列腺和前列腺增生上皮中的 TMPRSS2 表达显着升高（p < 0.01）。与模式 3 相比，TMPRSS2 表达在较高格里森级别的癌症（模式 4 和 5）中进一步升高 (p = 0.04)。此外，在大多数高级癌症中，TMPRSS2 定位错误，在细胞质和细胞膜中表达。前列腺癌转移通常也表达高水平的 TMPRSS2。总之，TMPRSS2 蛋白酶在原发性和转移性前列腺癌中高表达，并且与肿瘤细胞分化相关。根据对相关蛋白 matriptase 和 hepsin 的研究，应研究 TMPRSS2 在前列腺癌发生中的因果作用。版权所有 (C) 2008 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
Transmembrane serine protease 2 (TMPRSS2) is an androgen-regulated member of the type two transmembrane protease (TTSP) family. Two other members of the TTSP family, matriptase and hepsin, are over-expressed in prostate adenocarcinoma and mechanistically influence cancer cell invasion and metastasis. This study was performed to determine TMPRSS2 protein expression in primary and metastatic prostate cancers. We developed a monoclonal antibody capable of the sensitive and specific detection of TMPRSS2 protein. TMPRSS2 regulation by androgen and presence in seminal fluid was measured. TMPRSS2 localization and expression was evaluated in 415 cases of primary prostate cancer and 144 prostate cancer metastases by immunohistochemistry. We determined that TMPRSS2 protein expression is regulated by androgens and that TMPRSS2 is a component of the normal seminal fluid proteome. TMPRSS2 protein is abundantly expressed in the prostate, with low levels in the epithelia of the colon, stomach, epididymis and breast. Pancreatic acini, hepatic bile ducts, testicular Leydig cells and the kidney also express TMPRSS2. In the prostate, TMPRSS2 protein is specifically localized to the secretory epithelium, with enhanced expression in the plasma membrane orientated towards the ductal lumen. TMPRSS2 expression was significantly higher in both neoplastic prostate and in the epithelium of prostatic hyperplasia compared to normal epithelium (p < 0.01). TMPRSS2 expression was further elevated in higher Gleason grade cancers (patterns 4 and 5) compared to pattern 3 (p = 0.04). Furthermore, in most high-grade cancers, TMPRSS2 was mislocalized, being expressed in the cytoplasm as well as in the cell membrane. Prostate cancer metastases also generally expressed high levels of TMPRSS2. In summary, the TMPRSS2 protease is expressed highly in primary and metastatic prostate cancers and is associated with tumour cell differentiation. Based on studies with the related proteins matriptase and hepsin, TMPRSS2 should be investigated for causal roles in prostate carcinogenesis. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.