Abstract 1180: CCL-4 affects prostate cancer cell migration and tumorigenesis

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 19_Supplement; p. 1180
• Main Authors: Rohena-Rivera, Krizia, Sánchez-Vázquez, María M., Merly-Torres, Némesis, Casillas-González, Joseph A., Padín-López, Yarimar, Forestier-Román, Ingrid, Martínez-Ferrer, Magaly
• Format: Journal Article
• Language: English
• Published: 01.10.2014
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-1180

Abstract Prostate cancer (PCa) is the most frequently diagnosed and the second leading cause of cancer-related deaths in the United States. Inflammatory processes have been related to cancer progression and metastasis. Macrophage inflammatory protein 1β or CCL-4 has been reported as a differentially expressed chemokine among patients that showed PCa recurrence after radical prostastectomy. The aim of this study is to determine the role and mechanism of CCL-4 in the progression of PCa using in vitro and in vivo models. PC3 (androgen-independent) and 22RV1 (androgen-dependent) cell lines were treated in vitro with CCL-4 at concentrations of 0.001ng/mL and 0.1ng/mL and subjected to migration (Wound Healing) and invasion (Boyden Chamber) assays. The role of CCL-4 in PCa tumor progression was evaluated using a xenograft model in which the anterior prostate lobes of SCID mice were ortothopically injected with 250,000 22RV1 cells or 500,000 PC3 cells. CCL-4 was administered bi-weekly at concentrations of 0.001ng/mL and 0.1ng/mL with intraperitoneal injections during 4 weeks (22RV1) or 8 weeks (PC3). Tumor volumes were calculated using a caliper and tissue was collected, fixed and processed for gross examination, immunohistochemical, and gene expression analysis. In vitro studies indicated that PC3 cells treated with CCL4 had significantly increased migration when compared to control (P<0.05). Additionaly, in vivo, CCL-4 increased tumor volume when compared with tumors generated in mice treated with vehicle. Tumors developed with CCL-4 showed an increased expression of desmin, alpha-smooth muscle actin (α-sma), and phospho histone 3 (pH3). Gene expression analysis showed that CCL-4 modulates the expression of several genes involved in PCa progression including PTEN, β-Catenin, and matrix metalloproteinases. Real-Time PCR confirmed increased expression of MMP-11. This study shows that CCL4 alters migration of PC3 cells and 22RV1 cells in vitro. Additionally, CCL4 treatment induces tumor growth in vivo using a SCID mouse orthotopic model. Interestingly tumors treated with CCL4 were associated with increased levels of alpha smooth muscle actin, proliferation as well as increased levels of matrix metalloproteinases. Our results indicate that CCL4 may promote tumor growth and metastasis in vivo by increasing proliferation and altering migration. Citation Format: Krizia Rohena-Rivera, María M. Sánchez-Vázquez, Némesis Merly-Torres, Joseph A. Casillas-González, Yarimar Padín-López, Ingrid Forestier-Román, Magaly Martínez-Ferrer. CCL-4 affects prostate cancer cell migration and tumorigenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1180. doi:10.1158/1538-7445.AM2014-1180