PT  - JOURNAL ARTICLE
AU  - Benedek Bozóky
AU  - Carlos Fernández Moro
AU  - Carina Strell
AU  - Ingemar Ernberg
AU  - Laszlo Szekely
AU  - Marco Gerling
AU  - Béla Bozóky
TI  - Basal-to-classical phenotypic switch of pancreatic cancer cells upon integration into the duodenal epithelium
AID  - 10.1101/2021.02.01.429212
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.01.429212
4099  - http://biorxiv.org/content/early/2021/02/02/2021.02.01.429212.short
4100  - http://biorxiv.org/content/early/2021/02/02/2021.02.01.429212.full
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.