A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNF[alpha]-TGF[alpha]-EGFR
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摘要Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-[alpha]) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-[alpha]) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-[alpha] induces TGF-[alpha] transcription in stromal fibroblasts through nuclear factor-[kappa]B (NF-[kappa]B). We further show that TGF-[alpha] secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNF[alpha]-TGF[alpha]-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNF[alpha]-TGF[alpha]-EGFR.
著者Lau TS, Chan LKY, Wong ECH, Hui CWC, Sneddon K, Cheung TH, Yim SF, Lee JHS, Yeung CSY, Chung TKH, Kwong J
期刊名稱Oncogene
出版年份2017
月份6
卷號36
期次25
出版社Nature Publishing Group
出版地United Kingdom
頁次3576 - 3587
國際標準期刊號0950-9232
電子國際標準期刊號1476-5594
語言美式英語

上次更新時間 2020-30-06 於 04:28