Skip to main content

Research Repository

Advanced Search

A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFa-TGFa-EGFR.

Kwong

A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFa-TGFa-EGFR. Thumbnail


Authors



Abstract

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-a) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-a) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-a induces TGF-a transcription in stromal fibroblasts through nuclear factor-?B (NF-?B). We further show that TGF-a secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFa-TGFa-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 TNFa-TGFa-EGFR.

Citation

Kwong. (2017). A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFa-TGFa-EGFR. Oncogene, 3576 - 3587. https://doi.org/10.1038/onc.2016.509

Acceptance Date Dec 13, 2016
Publication Date Jun 22, 2017
Journal Oncogene
Print ISSN 1476-5594
Publisher Nature Publishing Group
Pages 3576 - 3587
DOI https://doi.org/10.1038/onc.2016.509
Keywords Lau, T-S.; Chan, L. K-Y.; Wong, E. C-H.; Hui, C. W-C.; Sneddon, K.; Cheung, T-H.; Yim, S-F.; Lee, J. H-S.; Yeung, C. S-Y.; Chung, T. K-H.; Kwong, J
Publisher URL https://www.nature.com/articles/onc2016509#Abs1

Files




You might also like



Downloadable Citations