human and mouse pancreatic cancer-associated stellate cells Transcriptome

Here, we show that primary cancer-associated PSCs (caPSCs) isolated from PDAC surgical specimens express a wild-type p53 protein that can be activated by the Mdm2 antagonist Nutlin-3a. Our work reveals that p53 acts as a major regulator of PSC activation and a modulator of PDAC fibrosis. In vitro, p53 activation by Nutlin-3a induces profound transcriptional changes and converts mouse and human activated PSCs to quiescence. In vivo, treatment of tumor-bearing mice with the clinical form of Nutlin-3a induces stromal p53 activation, reverses caPSCs activation and decreases fibrosis.