Abstract 996: Host-derived MCP-1 dictates prostate cancer skeletal metastasis in vivo

Autor: Jie Meng, Evan T. Keller, Weiping Liang, Haibo Tong, Jian Zhang, Yi Lu
Rok vydání: 2018
Předmět:
Zdroj: Cancer Research. 78:996-996
ISSN: 1538-7445
0008-5472
Popis: Overexpression of the tumor-derived monocyte chemotactic protein-1 (MCP-1) has been suggested to partially promote prostate cancer bone metastasis, but the function for host-derived MCP-1 in these processes is not well established. To understand the function of host-derived MCP-1 on bone metastasis, we developed a mouse model using intracardiac injection and in vivo selection to obtain tumor cell subpopulations with a higher propensity for bone metastasis. Here, we found that a loss of host MCP-1 (MCP-1 knockout) retarded tumor growth in bone and prolonged survival of mice by intracardiac injection of tumor cells in vivo. Moreover, a decrease in osteolytic bone lesion was observed in MCP-1 knockout mice by bone density analysis, as compared to wild-type control. Systemically, MCP-1 deficiency inhibited the proportion of PMN-and M-MDSC populations with immunosuppressive function. Together, this study indicates that the dysregulated immunity resulting from a loss of host MCP-1 signaling is sufficient to drive PCa bone metastasis, and provides a new perspective for targeting the endogenous MCP-1 pathway as an antimetastatic strategy. Supported by NSFC Key Project 81130046; NSFC projects 81773146, 81272415; JCYJ20170412152943794, JCYJ20170412154619484, JCYJ20170307105128101, JCYJ2017030711041760; Guangxi Key Projects 2013GXNSFEA053004. Citation Format: Jie Meng, Weiping Liang, Haibo Tong, Evan T. Keller, Jian Zhang, Yi Lu. Host-derived MCP-1 dictates prostate cancer skeletal metastasis in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 996.
Databáze: OpenAIRE