Abstract LB-294: Transforming growth factor beta 3 (TGF-ß3) contributes to epithelial-mesenchymal transitions (EMT) in human prostate cancer

Abstract Introduction and Objective: TGF-ß3 is considered as an important endogenous mediator of normal developmental and cellular repair, but its role in cancer is not well characterized. We recently reported that over-production of TGF-ß1 by tumor cells is involved in the epithelial-mesenchymal transition (EMT) in cancer cells. Based upon our prior findings, we hypothesized that, in addition to TGF-ß1, TGF-ß3 may also be involved in the EMT and contribute to prostate cancer (PCa) progression. In the present study, we explored the relationship between TGF-ß3 and TGF-ß1 induced EMT pathway in PCa. Methods: We studied 287 prostatectomy specimens obtained from the Northwestern University Prostate SPORE tissue bank. 165 specimens had low Gleason score (≤6, LGS), 55 had intermediate Gleason score (7, IGS), and 67 had high Gleason score (8-10, HGS). The median follow-up was 60 months (range 22-82). Levels of TGF-ß 1, TGF-ß 3, NF-kB and vimentin were analyzed using a high-throughput tissue microarray analysis and immunohistochemistry staining. Clinical correlation was performed based on patient follow-up information from the Prostate SPORE clinical-linked database which includes pre- and post-operative serum PSA levels. Results: High levels of TGF-ß3 expression were identified in 33.8%, 2.8% and 1.1% of HGS, IGS and LGS tumors, respectively, while high levels of vimentin expression occurred in 23.9%, 3.6% and 1.8% of HGS, IGS and LGS tumors, respectively. Expression of vimentin was significantly associated with high levels of TGF- ß3 (P=3.22E-06). Furthermore, TGF- ß3 overexpression was significantly associated with more aggressive tumors with high Gleason score (P=9.76E-09). Furthermore, there was a positive and significant correlation between expression of TGF- ß 3 and TGF-ß1 (P=2.29E-07), and between the expression levels of TGF- ß3 and NF-kB (P=7.52E-12), which were previously reported to be important mediators of the EMT in PCa. Conclusion: Our results firstly demonstrate that TGF-ß3 has a close correlation with TGF-ß 1 mediated overexpression of vimentin in PCa, which highly suggests that TGF-ß3 may play a critical role in the TGF- ß1 induced NF-kB mediated EMT signaling pathway. This pathway was reported to play a dramatic effect on the progression of human PCa and disease recurrence after prostatectomy. Consideration of TGF- ß3 tissue immunohistochemistry should be considered as a novel potential biomarker for EMT of PCa in clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-294. doi:1538-7445.AM2012-LB-294