早期研究證實(shí)TMPRSS4的過度表達(dá)與胰腺癌,、大腸癌和甲狀腺癌等類型癌癥的發(fā)生發(fā)展有關(guān)。TMPRSS4是一種細(xì)胞表面跨膜絲氨酸蛋白酶,，這一蛋白的表達(dá)對(duì)腫瘤細(xì)胞的遷移和轉(zhuǎn)移有作用,。
過去，有幾項(xiàng)研究探討了TMPRSS4基因表達(dá)水平以及蛋白產(chǎn)物,。最近刊登在Int J Oncol雜志上的一則研究中，研究人員用定量RT-PCR和蛋白質(zhì)染色來評(píng)估原發(fā)性非小細(xì)胞肺癌（NSCLC）組織和肺腫瘤細(xì)胞株中TMPRSS4的表達(dá)情況,。
結(jié)果發(fā)現(xiàn)在轉(zhuǎn)錄水平上,，正常肺組織相比，大多數(shù)人類鱗狀細(xì)胞癌和腺癌組織中TMPRSS4都顯著升高,。研究人員收集了超過100例非小細(xì)胞肺癌原發(fā)腫瘤和正常標(biāo)本,，用兔抗-TMPRSS4抗體染色證實(shí)在鱗狀細(xì)胞癌和腺癌組織中起蛋白表達(dá)水平較高，而在正常肺組織中很少或根本沒有染色的蛋白表達(dá),。
在體外研究中,，人源不同肺腫瘤細(xì)胞株表達(dá)TMPRSS4蛋白的水平式不一樣的。有趣的是,，TMPRSS4 mRNA表達(dá)水平高的腫瘤細(xì)胞株用免疫染色或流式細(xì)胞儀檢測(cè)時(shí),，卻檢測(cè)不到其蛋白表達(dá)。
然而,，腫瘤細(xì)胞在缺氧環(huán)境下培養(yǎng)時(shí),，TMPRSS4蛋白表達(dá)上調(diào)。這一結(jié)果證實(shí)體內(nèi)缺氧可能上調(diào)TMPRSS4蛋白表達(dá),?？偟膩碚f，這些結(jié)果表明,，在非小細(xì)胞肺癌中TMPRSS4蛋白過度表達(dá),，可能是一種潛在的治療靶點(diǎn)。（生物谷：Bioon.com）
doi:10.3892/ijo.2012.1513
PMC:
PMID:
Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia.
Nguyen TH, Weber W, Havari E, Connors T, Bagley RG, McLaren R, Nambiar PR, Madden SL, Teicher BA, Roberts B, Kaplan J, Shankara S.
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.
