Lau, T-S, Chan, LK-Y, Wong, EC-H, Hui, CW-C, Sneddon, K, Cheung, T-H, Yim, S-F, Lee, JH-S, Yeung, CS-Y, Chung, TK-H and Kwong, J ORCID: https://orcid.org/0000-0002-3380-6882 (2017) A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR. Oncogene, 36 (25). 3576 - 3587.

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

Item Type: Article
Additional Information: This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
Uncontrolled 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
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
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Depositing User: Symplectic
Date Deposited: 11 Mar 2020 10:57
Last Modified: 11 Mar 2020 10:57
URI: https://eprints.keele.ac.uk/id/eprint/7791

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