Expression of TMPRSS4 in non-small cell lung cancer and its modulation             by hypoxia.
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.
Genzyme Corporation, Framingham, MA 01701, USA. trihung.nguyen@genzyme.com
Tri-Hung
TH
Nguyen
William
W
Weber
Evis
E
Havari
Timothy
T
Connors
Rebecca G
RG
Bagley
Rajashree
R
McLaren
Prashant R
PR
Nambiar
Stephen L
SL
Madden
Beverly A
BA
Teicher
Bruce
B
Roberts
Johanne
J
Kaplan
Srinivas
S
Shankara
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D059016:Tumor Microenvironment; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D012333:RNA, Messenger; D012697:Serine Endopeptidases; C528837:TMPRSS4 protein, human; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases