Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia

Overexpression of TMPRSS4, a cell surface-associated transmembrane serineprotease, has been reported in pancreatic, colorectal and thyroid cancers, andhas been implicated in tumor cell migration and metastasis. Few reports have investigatedboth TMPRSS4 gene expression levels and the protein products. In this study, quantitativeRT-PCR and protein staining were used to assess TMPRSS4 expression in primarynon-small cell lung carcinoma (NSCLC) tissues and in lung tumor cell lines. Atthe transcriptional level, TMPRSS4 message was significantly elevated in the majorityof human squamous cell and adenocarcinomas compared with normal lung tissues.Staining of over 100 NSCLC primary tumor and normal specimens with rabbit polyclonalanti-TMPRSS4 antibodies confirmed expression at the protein level in both squamouscell and adenocarcinomas with little or no staining in normal lung tissues. Humanlung 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 TMPRSS4protein by either immunoblotting or flow cytometry. However, protein levels wereincreased under hypoxic culture conditions suggesting that hypoxia within thetumor microenvironment may upregulate TMPRSS4 protein expression in vivo. Thiswas supported by the observation of TMPRSS4 protein in xenograft tumors derivedfrom the cell lines. In addition, staining of human squamous cell carcinoma samplesfor carbonic anhydrase IX (CAIX), a hypoxia marker, showed TMPRSS4 positive cellsadjacent to CAIX positive cells. Overall, these results indicate that the cancer-associatedTMPRSS4 protein is overexpressed in NSCLC and may represent a potential therapeutictarget.