Abstract 1559: CCR5-CCRL2 regulates CCL5-induced organ specific metastasis: the in vitro and in vivo studies

Abstract

Abstract Previous studies of soluble factors in the tumor associated stromal cells demonstrated the elevation of CCL5 expression in prostate cancer patient sera that correlated wit malignant cancer progression. To evaluate the expression level of chemokine receptors in response to chemokines released by reactive stroma, quantitative PCR to evaluate the mRNA level of chemokine receptors was performed. We noticed the significant increased of CCRL2 (86-fold) and CXCR4 (45-fold) in androgen independent prostate cancer (AIPC) cells. This increased of CCRL2 expression also confirmed in malignant lung, breast and rental cells. Knockdown of CCRL2 declined 75% of migration activities induced by CCL5, suggests CCRL2 involve in CCL5 induce cancer migratory activities (t-test, p<0.001). IHC analysis of CCRL2 in paired prostate cancer patients was performed and revealed increasing of CCRL2 expression in malignant prostate cancer locus, whereas no CCRL2 can be detected in the benign region of same patient. Proximity ligation assays (PLAs) of benign, high grade tumor and tissues collected from patients less than 5-year survive demonstrated the PLA signals only in the lethal progression on patients. In vivo xenograft mice model studies demonstrated the organ specific cancer metastasis can be enhanced after overexpressed CCRL2 in cancer cells. Molecular analysis of CCRL2 demonstrated that CCRL2 regulated EZH2 expression in prostate cancer cells. In summary, out studies indicated the increased expression of CCRL2 play a central role in cancer cell migration induced by chemokine CCL5. The released of CCL5, secreted by bone stromal cells after interaction with dormancy cancer cell, may induce directional migration and invasion of circulating cancer cells. Clinical analyses demonstrated increased of CCRL2 in malignant prostate cancer. Inhibition of these homing mechanisms might significantly decreased cancer cell metastatic activities of AIPC patients. Citation Format: Chia-Ling Hsieh, Che-Ming Liu, Shian-Ying Sung. CCR5-CCRL2 regulates CCL5-induced organ specific metastasis: the in vitro and in vivo studies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1559.