Abstract B062: Proteomic characterization of the secretome from prostate cancer and bone progenitor cell coculture

Abstract

Abstract Prostate cancer (PCa) is one of the most frequent sites of primary tumor development in human beings. PCa tumor cells tend to disseminate to and form metastatic lesions in the bone. Given the evident prevalence and clinical significance of bone metastases, unraveling the mechanisms exploited by cancer to form these destructive lesions is of critical interest. This is partly due to the fact that the metastatic cascade encompasses many rate-limiting steps demanding tumor cells to employ new mechanisms at each stage. Our work aimed at evaluating which soluble factors could mediate the chemical crosstalk between PCa cells and bone progenitor cells. For this purpose, we used coculture transwell systems of PC3 (human PCa cells) with the preosteoclastic Raw264.7 or preosteoblastic MC3T3 cell lines (murine cells), where cells shared the culture media (CMs) without physical contact for 24h. We employed mass spectrometry—nanoLC-MS/MS(Orbitrap) —for the secretome analysis of the CMs. The obtained spectra were analyzed with the Proteome Discover Software and compared with both human and murine protein databases. Results highlight a differential secretome profile released to the CM when tumor cells are grown in coculture compared to controls. These results could potentially explain the altered mRNA expression levels assessed by RTqPCR in PCa cells growing in coculture, displaying significant upregulation for HO-1 ANXA2, ANXA2R, OPG, and PTHrP (p<0.05). Of note, coculture secretomes showcase highly bone-associated proteins released by tumoral cells such as periostin, cartilage oligomeric matrix protein, OPN, BMP and ILGF-II, IL-7, FGF, Mx-1—involved in prostate carcinogenesis—compared to controls, evidencing a misregulated microenvironment. These results may offer a better understanding of the molecular affinity between PCa cells and the bone microenvironment, allowing the improvement of PCa patient prognosis Citation Format: Nicolás Anselmino, Alejandra Páez, Sofía Lage Vickers, Javier Cotignola, Pía Valacco, Geraldine Gueron, Elba Vázquez. Proteomic characterization of the secretome from prostate cancer and bone progenitor cell coculture [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B062.