Abstract C166: Cancer cells expressing TMPRSS4 colocalized with carbonic anhydrase IX (CAIX)-positive cells in lung and pancreatic carcinomas

Abstract

Abstract TMPRSS4, a cell surface transmembrane serine protease, is over expressed at the transcriptional level in pancreatic, colorectal and thyroid cancers compared with normal tissues. Recent studies have indicated a role for TMPRSS4 in tumor cell migration and tumor metastasis. We examined TMPRSS4 expression in dissected non-small cell lung cancer (NSCLC) tissues by quantitative RT-PCR and immunohistochemisty. At the transcriptional level, TMPRSS4 expression was elevated in adeno and squamous cell (SC) carcinomas when compared to the matching normal tissues (p=0.0035). At the protein level, over 100 tumor and normal specimens were examined with rabbit polyclonal anti-TMPRSS4 antibodies via immunohistochemistry. Adeno and SC carcinomas were positive for TMPRSS4 (p<0.05), while little or no staining observed on the normal tissue sections. TMPRSS4 protein expression in tumor samples correlated with mRNA qRT-PCR results. When similar experiments were performed on lung cancer cell lines, six out of 16 lines expressed TMPRSS4 mRNA, particularly NCI-H358 and NCI-H596 cells which exhibited high TMPRSS4 message with an average of 6000 and 5000 copies, respectively, relative to the 18S rRNA; however, no TMPRSS4 protein was detected either by Western blot or flow cytometry. When NCI-H358 cells were implanted into nude mice, TMPRSS4 was detected in the xenograft tumors via immunohistochemistry. When lung SC carcinoma and pancreatic adenocarcinoma were stained for TMPRSS4 and for the hypoxia marker, CAIX, TMPRSS4 positive cells were found to be adjacent to CAIX positive cells; however, no co-staining in the same cell was observed, suggesting that TMPRSS4 has a significant function with the adjacent hypoxic cancer cells in tumor tissues, and hypoxia may induce TMPRSS4 expression in xenograft tumors of NCI-H358 in which protein is not detectable under normal cell culture environment. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C166.