Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology

Background: Mortality rates in lung cancer patients have not decreased significantly in recent years, even with the implementation of new therapeutic regimens. One of the main problems is that a large proportion of patients present local or distant metastasis at the time of diagnosis. The need for i...

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Bibliographic Details
Published in:British journal of cancer 2011-11, Vol.105 (10), p.1608-1614
Main Authors: Larzabal, L, Nguewa, P A, Pio, R, Blanco, D, Sanchez, B, Rodríguez, M J, Pajares, M J, Catena, R, Montuenga, L M, Calvo, A
Format: Article
Language:English
Subjects:
692/699/67/1612/1350
692/699/67/1857
692/700/1750
Aged
Animals
Biological and medical sciences
Biomarkers, Tumor - genetics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Drug Resistance
Epidemiology
Female
Humans
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Medical sciences
Membrane Proteins - genetics
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Molecular Diagnostics
Molecular Medicine
Neoplasm Metastasis
Oncology
Pneumology
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Serine Endopeptidases - genetics
Tumors
Tumors of the respiratory system and mediastinum
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Summary:Background: Mortality rates in lung cancer patients have not decreased significantly in recent years, even with the implementation of new therapeutic regimens. One of the main problems is that a large proportion of patients present local or distant metastasis at the time of diagnosis. The need for identification of novel biomarkers and therapeutic targets for a more effective management of lung cancer led us to investigate TMPRSS4, a protease reported to promote tumour growth and metastasis. Material and methods: In all, 34 lung cancer cell lines were used to evaluate the TMPRSS4 expression. Cell migration and clonogenic assays, and an in-vivo lung metastasis model were used for functional analysis of the TMPRSS4 downregulation in H358, H441 and H2170 cell lines. The TMPRSS4 expression analysis in normal and malignant lung tissue samples was performed by qPCR. Five different microarray-based publicly available expression databases were used to validate our results and to study prognosis. Results: The TMPRSS4 knock down in H358, H441 and H2170 cells resulted in a significant reduction in proliferation, clonogenic capacity and invasion. A significant ( P 30-fold increase ( P
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2011.432