Abstract
identified IL-8 signalling and the wnt-β-catenin pathway as the key canonical pathways affected. Organotypic co-culture of PSCs and cancer cells demonstrated an indirect effect of treated PSCs on cancer cell morphology, proliferation (decrease) and apoptosis (increase) and confirmed the engagement of the wnt-β-catenin signalling pathway. There was less βcatenin signalling (TOPFlash reporter assays) in cancer cells co-cultured with treated quiescent PSCs, which was mediated by an increased expression of sFRP4 (secreted frizzledrelated protein 4) resulting in decreased invasion of cancer cells. Additionally, in contrast to vehicle treated orgnaotypic cultures, PSCs exposed to ATRA did not invade into the extracellular matrix gel but formed a “wall” at the cancer-matrix junction, blocking cancer cell invasion. Conclusion: Targeting the desmoplastic stroma with agents such as ATRA interferes with the, for tumour progression important, tumour-stroma cross-talk and offers exciting opportunities for combinatorial therapy for pancreatic cancer.
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