Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

YKL40 as a therapeutic target for the treatment of castration resistant prostate cancer (#76)

Varinder Jeet 1 , Colleen Nelson 1
  1. Queensland University of Technology, Woolloongabba, Qld, Australia

Prostate cancer (PCa) is the most commonly diagnosed lethal cancer and the second leading cause of cancer-related deaths in Australian men with a total of 20,000 new cases and 3,300 deaths annually. Androgen Deprivation Therapy (ADT) is the mainstay therapy for advanced PCa and leads to 1-3 years of remission, but the disease ultimately progresses to a stage of castration resistant PCa (CRPC) which is currently incurable. Angiogenesis plays a fundamental role in promoting tumour growth and thereby anti-angiogenesis therapy has been seen as a promising approach for treating patients with CRPC disease. Our focus in this project is to explore the biological significance of a potential angiogenic target, YKL40. Methods: YKL40 mRNA and protein expression profiles were analysed in different PCa cell lines representing progressive stages of human disease. siRNA mediated YKL40 specific knockdown was performed in LNCaP, C42, and C42-B cell lines and the effects on markers of angiogenesis, metastasis, and radioresistance were analysed by real time PCR and western blotting. Results:  The results show that gene and protein expression of YKL40 increases in cell lines representative of advanced disease as compared to less aggressive cancer. Moreover, cells treated with YKL40 siRNA show downregulation of classical markers of angiogenesis and metastasis, such as VEGF-A, angiogenin and MMP-9. However, the expression of E-cadherin increases after YKL40 knockdown. We have also observed that YKL40 regulates the expression of NNMT, a gene overexpressed in a number of cancers, and is involved in radioresistance. Conclusion: Our preliminary results suggest the potential role of YKL40 in processes related to cell survival and growth and warrants further investigation. This has the potential to lead to a new targeting approach for therapeutic intervention in advanced therapy-resistant prostate cancers that have thus far proved difficult to treat.