Journal
BRITISH JOURNAL OF CANCER
Volume 100, Issue 11, Pages 1784-1793Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6605089
Keywords
inhibin-alpha subunit; prostate cancer; metastasis; androgen independent
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Funding
- United States Department of Defense
- Cancer Council Victoria
- Cancer Institute of New South Wales
- Australian National Health and Medical Research Council (NHMRC)
- Pfizer Foundation
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The biological function of inhibin-alpha subunit (INH alpha) in prostate cancer (PCa) is currently unclear. A recent study associated elevated levels of INH alpha in PCa patients with a higher risk of recurrence. This prompted us to use clinical specimens and functional studies to investigate the pro-tumourigenic and pro-metastatic function of INH alpha. We conducted a cross-sectional study to determine a link between INH alpha expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and vascular endothelial growth factor receptor-3 expression, which are well-established prognostic factors of PCa. In addition, using two human PCa cell lines (LNCaP and PC3) representing androgen-dependent and -independent PCa respectively, we investigated the biological function of elevated levels of INH alpha in advanced cancer. Elevated expression of INH alpha in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. Over-expressing INH alpha in LNCaP and PC3 cells demonstrated two different and cell-type-specific responses. INH alpha-positive LNCaP demonstrated reduced tumour growth whereas INH alpha-positive PC3 cells demonstrated increased tumour growth and metastasis through the process of lymphangiogenesis. This study is the first to demonstrate a pro-tumourigenic and pro-metastatic function for INH alpha associated with androgen-independent stage of metastatic prostate disease. Our results also suggest that INH alpha expression in the primary prostate tumour can be used as a predictive factor for prognosis of PCa. British Journal of Cancer (2009) 100, 1784-1793. doi: 10.1038/sj.bjc.6605089 www.bjcancer.com Published online 12 May 2009 (C) 2009 Cancer Research UK
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