Abstract IA-18: Epithelial cell plasticity in pancreatic cancer: The function and fate of metaplastic tuft cells

Abstract

Abstract The pancreas is a notoriously plastic organ. In pancreatitis and early in the transformation process, pancreatic acinar cells give rise to a relatively homogeneous metaplastic duct phenotype. By modulating developmental transcription factor networks metaplastic duct cells then transdifferentiate to other epithelial derivatives including chemosensory tuft cells and neuroendocrine-like adenocarcinoma. To determine the function of metaplastic tuft cells (MTCs), we ablated the taste receptor associated G-protein GNAT3 in the context of pancreatic neoplasia. We found an accelerated progression of benign pancreatic neoplasia to pancreatic cancer, a phenotype attributable to a reactive upregulation of CXCL1 and CXCL2, and a resulting influx of immunosuppressive granulocytic MDSCs. To determine the fate of MTCs, we used a novel dual recombinase system to lineage trace their fate through pancreatic cancer progression, finding that they give rise to a unique subset of cells within invasive adenocarcinoma. Citation Format: Howard C. Crawford. Epithelial cell plasticity in pancreatic cancer: The function and fate of metaplastic tuft cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-18.