Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Epithelial and Mesenchymal Pancreatic Cancer Cells Exhibit Different Stem Cell Phenotypes Being Associated with Different Metastatic Propensity

Lisa-Marie Philipp
ORCID logo ,
Umut-Ulas Yesilyurt
,
Arne Surrow
,
Axel Künstner
,
Anne-Sophie Mehdorn
ORCID logo ,
Charlotte Hauser
,
Jan-Paul Gundlach
ORCID logo ,
Olga Will
,
Patrick Hoffmann
,
Lea Stahmer
,
Sören Franzenburg
,
Hendrike Knaack
,
Udo Schumacher
,
Hauke Busch
ORCID logo ,
Susanne Sebens
* ORCID logo
Version 1 : Received: 15 November 2023 / Approved: 16 November 2023 / Online: 16 November 2023 (11:36:00 CET)

A peer-reviewed article of this Preprint also exists.

Philipp, L.-M.; Yesilyurt, U.-U.; Surrow, A.; Künstner, A.; Mehdorn, A.-S.; Hauser, C.; Gundlach, J.-P.; Will, O.; Hoffmann, P.; Stahmer, L.; Franzenburg, S.; Knaack, H.; Schumacher, U.; Busch, H.; Sebens, S. Epithelial and Mesenchymal-like Pancreatic Cancer Cells Exhibit Different Stem Cell Phenotypes Associated with Different Metastatic Propensities. Cancers 2024, 16, 686. Philipp, L.-M.; Yesilyurt, U.-U.; Surrow, A.; Künstner, A.; Mehdorn, A.-S.; Hauser, C.; Gundlach, J.-P.; Will, O.; Hoffmann, P.; Stahmer, L.; Franzenburg, S.; Knaack, H.; Schumacher, U.; Busch, H.; Sebens, S. Epithelial and Mesenchymal-like Pancreatic Cancer Cells Exhibit Different Stem Cell Phenotypes Associated with Different Metastatic Propensities. Cancers 2024, 16, 686.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages limiting patient´s prognosis. Metastasis requires high tumor cell plasticity implying phenotypic switching in response to changing environments. Here, Epithelial-Mesenchymal-Transition (EMT), being associated with the gain of cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC-phenotypes exist along the EMT-axis and how these impact malignancy-associated properties, we aimed to characterize CSC-populations of epithelial and mesenchymal PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. Panc1 Holoclone cells showed a mesenchymal phenotype dominated by high expression of the stemness marker Nestin, while Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. Panc89 Holoclone cells showed enhanced cell growth and self-renewal capacity but slow cluster-like invasion. Contrarily, Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, Panc1 and Panc89 cell variants significantly differed regarding number and size of metastases as well as organ manifestation leading to different survival outcomes. Overall, these data support the existence of different CSC-phenotypes along the EMT-axis in PDAC manifesting in different metastatic propensities.

Keywords

Pancreatic adenocarcinoma, PDAC, cancer stem cells, EMT, Epithelial-Mesenchymal-Transition, Heterogeneity, Plasticity, Adhesion, Migration, Invasion, Metastasis

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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