| Literature DB >> 31705064 |
Chaoyang Sun1, Xi Li1, Ensong Guo1, Na Li1,2, Bo Zhou1,3, Hao Lu1,4, Jia Huang1, Meng Xia1,4, Wanying Shan1, Beibei Wang1, Kezhen Li1, Danhui Weng1, Xiaoyan Xu1, Qinglei Gao1, Shixuan Wang1, Junbo Hu1,5, Yiling Lu6, Gordon B Mills6, Gang Chen7.
Abstract
Ovarian cancer selective metastasizes to the omentum contributing to the poor prognosis associated with ovarian cancer. However, the mechanism underlining this propensity and therapeutic approaches to counter this process has not been fully elucidated. Here, we show that MCP-1 produced by omental adipocytes binding to its cognate receptor CCR-2 on ovarian cancer cells facilitates migration and omental metastasis by activating the PI3K/AKT/mTOR pathway and its downstream effectors HIF-1α and VEGF-A in cell lines, xenografts, and transgenic murine models. MCP-1 antibody significantly decreased tumor burden and increased survival of mice in vivo. Interestingly, metformin decreased omental metastasis at least partially by inhibiting MCP-1 secretion from adipocytes independent of direct effects on cancer cells. Together this suggests a novel target of MCP-1/CCR-2 axis that could benefit ovarian cancer patients.Entities:
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Year: 2019 PMID： 31705064 PMCID： PMC8290627 DOI： 10.1038/s41388-019-1090-1
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867