Elevated level of inhibin-alpha subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer.

Abstract

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.

• Authors: P Balanathan, E D Williams, H Wang, J S Pedersen, L G Horvath, M G Achen, S A Stacker, G P Risbridger
• Journal: British journal of cancer (Br J Cancer) Vol. 100 Issue 11 Pg. 1784-93 (Jun 02 2009) ISSN: 1532-1827 [Electronic] England
• PMID: 19436293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• inhibin-alpha subunit
• Inhibins

Topics

• Adenocarcinoma (metabolism, pathology)
• Cell Line, Tumor
• Cell Separation
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Inhibins (genetics, metabolism)
• Male
• Neoplasm Metastasis (genetics, pathology)
• Neoplasm Staging
• Prostatic Neoplasms (genetics, metabolism, pathology)