RT Journal Article
SR Electronic
T1 Basal-to-classical phenotypic switch of pancreatic cancer cells upon integration into the duodenal epithelium
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.01.429212
DO 10.1101/2021.02.01.429212
A1 Benedek Bozóky
A1 Carlos Fernández Moro
A1 Carina Strell
A1 Ingemar Ernberg
A1 Laszlo Szekely
A1 Marco Gerling
A1 Béla Bozóky
YR 2021
UL http://biorxiv.org/content/early/2021/02/02/2021.02.01.429212.abstract
AB Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes can be defined that differ in prognosis. Single-cell sequencing has recently revealed that these subtypes coexist in individual tumors. However, the contribution of either clonal heterogeneity or microenvironmental cues to subtype heterogeneity is unclear. Here, we report the tumor phenotype dynamics in a cohort of patients in whom PDAC infiltrated the duodenal wall. Using multiplex immunohistochemistry, we show that PDAC cells revert to non-destructive growth and undergo differentiation towards the classical subtype upon integration into the duodenal epithelium. Our results tightly link microenvironmental cues to the PDAC molecular subtype and open the door to a systematic investigation of microenvironmental control in human pancreatic cancer.Competing Interest StatementThe authors have declared no competing interest.