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- W4250514543 abstract "Background: We investigated the tumor-stroma interplay and the role of the transcription factor Zinc finger E-box binding homeobox 1 (ZEB1) in pancreatic ductal adenocarcinoma (PDAC) and evaluated the prognostic value of cancer associated fibroblasts (CAF). Methods: A standard pathology protocol, including CAF activation assessment as either Grade 0 or Grade +, was applied for specimen of patients operated for PDAC. Interaction between a spectrum of pancreatic cancer cell lines and mouse embryonic fibroblasts (NIH 3T3) was assessed in a conditioned medium experimental set-up. Results: N=119 patients were analysed. In univariate analysis CAF + was negatively associated with survival (p=.032) and positively correlated with nuclear ZEB1 expression in cells from the tumor center (p=.001), high T-status (p=.025) and tumor grade (p=.017). Medium conditioned by pancreatic cancer cells (PCC-CM) led to a spindle-like morphology and increased proliferation in NIH 3T3 fibroblasts. Paracrine effects of NIH 3T3 fibroblasts promoted motility in all PCC. PCC-CM by poorly differentiated PCC led to a higher expression of vimentin in NIH 3T3 cells, whereas PCC-CM by well-differentiated PCC led to a down-regulation. NIH 3T3 fibroblast matrix decreased the proliferation of all PCC and led to up-regulation of ZEB1. Conclusion: CAF is a negative prognostic factor for PDAC. Physical growth limitation by stromal matrix leads to a ZEB1 upregulation, suggesting an interlink of stromal activation and epithelial-mesenchymal transition processes." @default.
- W4250514543 created "2022-05-12" @default.
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- W4250514543 date "2019-01-01" @default.
- W4250514543 modified "2023-10-18" @default.
- W4250514543 title "Extensive desmoplasia is associated with high expression of ZEB1 in pancreatic cancer cells and cancer associated fibroblasts determine prognosis" @default.
- W4250514543 doi "https://doi.org/10.1016/j.hpb.2019.10.955" @default.
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