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A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR
Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumour-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 tumour necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodelling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-kB (NF-kB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signalling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumour 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.
Date:
26 July 2017, 15:30
Venue:
MRC Weatherall Institute of Molecular Medicine, Headington OX3 9DS
Venue Details:
Seminar Room
Speaker:
Dr Joseph Kwong (Chinese University of Hong Kong)
Organising department:
Department of Oncology
Organiser:
Penny Berry (University of Oxford, Department of Oncology, Weatherall Institute of Molecular Medicine)
Organiser contact email address:
penny.berry@oncology.ox.ac.uk
Host:
Dr Ahmed Ahmed (University of Oxford)
Part of:
WIMM Occasional Seminars
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Penny Berry
