Open Access

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

  • Authors:
    • Tri-Hung Nguyen
    • William Weber
    • Evis Havari
    • Timothy Connors
    • Rebecca G. Bagley
    • Rajashree McLaren
    • Prashant R. Nambiar
    • Stephen L. Madden
    • Beverly A. Teicher
    • Bruce Roberts
    • Johanne Kaplan
    • Srinivas Shankara
  • View Affiliations

  • Published online on: June 12, 2012     https://doi.org/10.3892/ijo.2012.1513
  • Pages: 829-838
  • Copyright: © Nguyen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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.
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September 2012
Volume 41 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Nguyen T, Weber W, Havari E, Connors T, Bagley RG, McLaren R, Nambiar PR, Madden SL, Teicher BA, Roberts B, Roberts B, et al: Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia. Int J Oncol 41: 829-838, 2012.
APA
Nguyen, T., Weber, W., Havari, E., Connors, T., Bagley, R.G., McLaren, R. ... Shankara, S. (2012). Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia. International Journal of Oncology, 41, 829-838. https://doi.org/10.3892/ijo.2012.1513
MLA
Nguyen, T., Weber, W., Havari, E., Connors, T., Bagley, R. G., McLaren, R., Nambiar, P. R., Madden, S. L., Teicher, B. A., Roberts, B., Kaplan, J., Shankara, S."Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia". International Journal of Oncology 41.3 (2012): 829-838.
Chicago
Nguyen, T., Weber, W., Havari, E., Connors, T., Bagley, R. G., McLaren, R., Nambiar, P. R., Madden, S. L., Teicher, B. A., Roberts, B., Kaplan, J., Shankara, S."Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia". International Journal of Oncology 41, no. 3 (2012): 829-838. https://doi.org/10.3892/ijo.2012.1513