New Action of Inhibin Alpha Subunit in Advanced Prostate Cancer
Abstract
This project ultimately aimed to identify the role of inhibin alpha (INHA) in advanced prostate cancer. The hypothesis tested was that INHA is tumor promoting and pro-metastatic in advanced prostate cancer (PCa). At the end of this project, we have made significant progress towards understanding the role INHA in advanced prostate disease. We have demonstrated that increased INHA expression in highly aggressive, metastatic and androgen-independent PCa cell line, PC3, further promotes its tumor growth and metastatic ability. Increase in metastasis was further evident by increase lymph vessel density (LVD) and lymphatic invasion by the cancer cells. This was also accompanied by increase in VEGF-A and VEGF-C expression. In vitro tube formation assays has shown that Inhibin B and not Inhibin A induces significant lymphatic endothelial cell (LEC) tube formation. Furthermore, we conducted a cross-sectional study to determine a link between INHA expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and VEGF-R3 expression which are well established prognostic factors of PCa. Elevated expression of INHA in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. This study is the first to demonstrate a pro-tumorigenic and prometastatic role for INHA in the androgen-independent stage of metastatic prostate disease. Our results also suggest that INHA expression in the primary prostate tumor can be used as a predictive factor for prognosis of PCa.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2010
- Accession Number
- ADA524584
Entities
People
- Preetika Balanathan
Organizations
- Monash University