Genzyme Corporation, Framingham, MA 01701, USA.
Int J Oncol. 2012 Sep;41(3):829-38. doi: 10.3892/ijo.2012.1513. Epub 2012 Jun 12.
Overexpression of TMPRSS4, a cell surface-associated transmembrane serine protease, has been reported in pancreatic, colorectal and thyroid cancers, and has been implicated in tumor cell migration and metastasis. Few reports have investigated both TMPRSS4 gene expression levels and the protein products. In this study, quantitative RT-PCR and protein staining were used to assess TMPRSS4 expression in primary non-small cell lung carcinoma (NSCLC) tissues and in lung tumor cell lines. At the transcriptional level, TMPRSS4 message was significantly elevated in the majority of human squamous cell and adenocarcinomas compared with normal lung tissues. Staining of over 100 NSCLC primary tumor and normal specimens with rabbit polyclonal anti-TMPRSS4 antibodies confirmed expression at the protein level in both squamous cell and adenocarcinomas with little or no staining in normal lung tissues. Human lung tumor cell lines expressed varying levels of TMPRSS4 mRNA in vitro. Interestingly, tumor cell lines with high levels of TMPRSS4 mRNA failed to show detectable TMPRSS4 protein by either immunoblotting or flow cytometry. However, protein levels were increased under hypoxic culture conditions suggesting that hypoxia within the tumor microenvironment may upregulate TMPRSS4 protein expression in vivo. This was supported by the observation of TMPRSS4 protein in xenograft tumors derived from the cell lines. In addition, staining of human squamous cell carcinoma samples for carbonic anhydrase IX (CAIX), a hypoxia marker, showed TMPRSS4 positive cells adjacent to CAIX positive cells. Overall, these results indicate that the cancer-associated TMPRSS4 protein is overexpressed in NSCLC and may represent a potential therapeutic target.
跨膜丝氨酸蛋白酶 4（TMPRSS4）的过表达已在胰腺癌、结直肠癌和甲状腺癌中报道，并与肿瘤细胞迁移和转移有关。很少有报道同时研究 TMPRSS4 基因表达水平和蛋白产物。在这项研究中，使用定量 RT-PCR 和蛋白染色来评估原发性非小细胞肺癌（NSCLC）组织和肺肿瘤细胞系中的 TMPRSS4 表达。在转录水平上，与正常肺组织相比，大多数人鳞状细胞癌和腺癌中的 TMPRSS4 消息明显升高。用兔多克隆抗 TMPRSS4 抗体对超过 100 个 NSCLC 原发性肿瘤和正常标本进行染色，在鳞状细胞癌和腺癌中证实了蛋白水平的表达，而在正常肺组织中则几乎没有或没有染色。人肺肿瘤细胞系在体外表达不同水平的 TMPRSS4 mRNA。有趣的是，TMPRSS4 mRNA 水平高的肿瘤细胞系通过免疫印迹或流式细胞术均未能检测到 TMPRSS4 蛋白。然而，在低氧培养条件下蛋白水平增加，提示肿瘤微环境中的缺氧可能上调体内 TMPRSS4 蛋白表达。这得到了来自细胞系的异种移植肿瘤中 TMPRSS4 蛋白观察结果的支持。此外，对人鳞状细胞癌样本进行碳酸酐酶 IX（CAIX）染色，一种缺氧标志物，显示 TMPRSS4 阳性细胞与 CAIX 阳性细胞相邻。总的来说，这些结果表明，与癌症相关的 TMPRSS4 蛋白在 NSCLC 中过度表达，可能代表一个潜在的治疗靶点。
