Stabilization of the classical phenotype upon integration of pancreatic cancer cells into the duodenal epithelium

• DOI: 10.1016/j.neo.2021.11.007
• Publication Date: 2021-11-16T18:23:16Z
• Authors: Benedek Bozóky; Carlos Fernández ...; Carina Strell; Natalie Geyer; Rainer L. Heuchel; J. Matthias Löhr; Ingemar Ernberg; Laszlo Szekely; Marco Gerling; Béla Bozóky
• Keywords: Gastrointestinal epithelium; Duodenal cancer

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes have been defined that differ in prognosis. Cells both can coexist individual tumors; however, contribution either clonal heterogeneity or microenvironmental cues to subtype unclear. Here, we report spatial tumor phenotype dynamics a cohort patients whom infiltrated duodenal wall, identify epithelium as distinct microniche. Materials methods: We used serial multiplex quantitative immunohistochemistry (smq-IHC) for 24 proteins phenotypically chart cells whose tumors epithelium. Additionally, genetically engineered mouse model study cell small intestinal controlled genetic background. Result: show pancreatic cancer revert non-destructive growth upon integration into epithelium, where they adopt traits differentiation, associated with phenotypical stabilization subtype. The integrated replace epithelial an adenoma-like manner, opposed invasive submucosa. Finally, this phenomenon shared between species, by confirming phenotypic switching model. Discussion: Our results microniche tightly link cue transcriptional subtypes. "intestinal mimicry" provides unique opportunity systematic investigation influences plasticity.