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Basal-to-classical phenotypic switch of pancreatic cancer cells upon integration into the duodenal epithelium

Benedek Bozóky, Carlos Fernández Moro, Carina Strell, Ingemar Ernberg, Laszlo Szekely, Marco Gerling, Béla Bozóky
doi: https://doi.org/10.1101/2021.02.01.429212
Benedek Bozóky
1Theme Cancer, oncology, Karolinska University Hospital, 17 176 Solna, Sweden
2Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden
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  • For correspondence: marco.gerling@ki.se benedek.bozoky@ki.se
Carlos Fernández Moro
3Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, 14186, Sweden
4Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 14186 Stockholm, Sweden
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Carina Strell
5Department of Oncology-Pathology, Karolinska Institutet, 17164 Solna, Sweden
6Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden
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Ingemar Ernberg
2Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden
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Laszlo Szekely
3Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, 14186, Sweden
4Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 14186 Stockholm, Sweden
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Marco Gerling
1Theme Cancer, oncology, Karolinska University Hospital, 17 176 Solna, Sweden
7Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Sweden
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  • For correspondence: marco.gerling@ki.se benedek.bozoky@ki.se
Béla Bozóky
3Department of Clinical Pathology/Cytology, Karolinska University Hospital, Stockholm, 14186, Sweden
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Abstract

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 Statement

The authors have declared no competing interest.

Footnotes

  • ↵* shared authorship

  • Conflicts of Interest: The authors declare that no conflicts of interest exist.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 02, 2021.
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Basal-to-classical phenotypic switch of pancreatic cancer cells upon integration into the duodenal epithelium
Benedek Bozóky, Carlos Fernández Moro, Carina Strell, Ingemar Ernberg, Laszlo Szekely, Marco Gerling, Béla Bozóky
bioRxiv 2021.02.01.429212; doi: https://doi.org/10.1101/2021.02.01.429212
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Basal-to-classical phenotypic switch of pancreatic cancer cells upon integration into the duodenal epithelium
Benedek Bozóky, Carlos Fernández Moro, Carina Strell, Ingemar Ernberg, Laszlo Szekely, Marco Gerling, Béla Bozóky
bioRxiv 2021.02.01.429212; doi: https://doi.org/10.1101/2021.02.01.429212

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