Abstract 391: Inflammatory mediators of prostate cancer metastasis

Abstract

Abstract Inflammation has been linked to the initiation and metastatic progression of prostate cancer. We previously reported results showing that CX3CL1 and IL-15 were predominantly down-regulated in prostate cancer patients that develop biochemical recurrence following prostatectomy. This study tests the hypothesis that chemokine biomarkers that predict biochemical recurrence of prostate cancer regulate metastatic progression of the cancer. In order to determine the function of the chemokines, PC3 and LNCaP prostate cancer cell lines were used alone and in combination with conditioned media from prostate stromal cells expressing the chemokines of interest. IL-15 and CX3CL1 cDNAs were subcloned into lentiviral constructs. The lentiviral constructs were transduced into prostate stromal cells developed from wild type C57BL/6 mice. Seventy-two hours conditioned media was used to verify the expression of the respective chemokines by ELISA. The individual prostate cancer cell lines (PC3 and LNCaP) were incubated in the respective stromal conditioned media and characterized for measurable characteristics that promote a cancer cell to be metastatic. In this study we show that IL-15 and CX3CL1 significantly decreased (P<0.0001) PC3 proliferation in vitro. Furthermore, IL-15 and CX3CL1 also had the ability to significantly inhibit migration of PC3 prostate cancer cells in vitro (P<0.01). Introducing IL-15 and CX3CL1 into the stromal microenvironment of the androgent independent PC3 cells significantly increased apoptosis (P<0.05). No significant changes were observed in the androgen dependent LNCaP prostate cancer cells. Our results indicate that IL-15 and CX3CL1 may suppress metastasis in vitro by decreasing proliferation and migration, and increasing apoptosis in the highly metastatic PC3 prostate cancer cell line. The studies will help to enable the dissection of the role of the chemokines on cancer cells in the context of its stromal micronvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 391. doi:10.1158/1538-7445.AM2011-391