Abstract 2877: Dual role of mast cells in prostate tumors.

Abstract

Abstract Prostatic carcinoma is most often a multifocal disease, with areas of localized, well-differentiated adenocarcinomas coexisting with poorly differentiated lesions within the same tumor. Mast cells (MC), classically known as the primary responders in allergic reactions, have been recently indicate of prognostic value in prostate cancer. We have evidence of a dual role of MC in prostate cancer. Within the same human tumor, MC are specifically enriched and degranulated in areas of adenocarcinoma, whereas few around anaplastic foci. This observation has been confirmed in tumors from TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) mice, and in two novel tumor cells lines, derived from them, phenocopying well and poorly differentiated adenocarcinoma: T1525 and T23, respectively. MC promote the growth of the well-differentiated adenocarcinoma T1525 that does not develop when transplanted into MC-deficient mice, or when MC degranulation is pharmacologically inhibited with sodium cromoglycate. In particular, mast cells are essential for the outgrowth of early-stage tumors due to their matrix metalloproteinase-9 production, become dispensable in advanced-stage, post-epithelial-to-mesenchymal transition, and are protective against neuroendocrine prostate tumor variants. Indeed, pharmacological inhibition or genetic ablation of MC in TRAMP mice results in early development of undifferentiated tumors characterized by marked anaplasia, suggesting that the growth of anaplastic clones may be antagonized by MC. Our data demonstrate that MC can influence the histotype of tumor arising from the prostate and that their targeting may change tumor outcome. As a possible corollary, MC depletion might favor the growth of more undifferentiated and aggressive variants. The common expression of c-Kit by mast cells and neuroendocrine clones suggests a possible competition for the ligand Stem Cell Factor and offers the chance of curing early-stage disease while preventing neuroendocrine tumors using c-Kit-targeted therapy. Citation Format: Mario P. Colombo, Paola Pittoni, Sabina Sangaletti, Claudio Tripodo. Dual role of mast cells in prostate tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2877. doi:10.1158/1538-7445.AM2013-2877