Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition

Journal of Cancer Research and Clinical Oncology · 7 authors, 2 centres

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This preclinical in vitro study used murine pancreatic cancer cell lines cultured with conditioned media from glial cells. It found that glial cell-derived factors increased cancer cell invasiveness and migration, induced markers of epithelial-to-mesenchymal transition, and increased resistance to the chemotherapy drug gemcitabine.

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This preclinical, in vitro study investigated the influence of glial cell-derived soluble factors on murine pancreatic ductal adenocarcinoma (PDAC) cell lines (Panc02, UN-KC-6141). Cancer cells were cultured with conditioned media (CM) from primary enteric glial cells (EGCs) or the IMS32 Schwann cell line. The study measured effects on invasiveness, migration, proliferation, viability, gene expression, and drug resistance. Central results showed that glial cell CM increased the migratory capacity and invasiveness of PDAC cells. It induced an epithelial-to-mesenchymal transition (EMT) phenotype, evidenced by decreased E-cadherin and increased N-cadherin and Vimentin levels, with the transcription factor Snail upregulated. Glial cell CM also inhibited PDAC cell proliferation while preserving viability, suggesting a quiescent state, and increased their resistance to gemcitabine. The study concluded that glial cells can enhance the metastatic potential and chemoresistance of PDAC cells through these mechanisms, highlighting potential implications for therapeutic strategies.

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other

SPECIALTY

oncology

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ORIGINAL PAPER

PMC10590291

Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition

Journal of Cancer Research and Clinical Oncology

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ABSTRACT

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, characterized by the spreading of highly metastatic cancer cells, including invasion into surrounding nerves and perineural spaces. Nerves, in turn, can invade the tumor tissue and, through the secretion of neurotrophic factors, chemokines, and cytokines, contribute to PDAC progression. However, the contribution of the nerve-associated glial cells to PDAC progression is not well characterized. Methods Two murine PDAC cell lines were cultured with the conditioned media (CM) of primary enteric glial cells or IMS32 Schwann cells (SCs). Different properties of PDAC cells, such as invasiveness, migratory capacity, and resistance to gemcitabine, were measured by RT-qPCR, microscopy, and MTT assays. Using a neuronal cell line, the observed effects were confirmed to be specific to the glial lineage. Results Compared to the control medium, PDAC cells in the glial cell-conditioned medium showed increased invasiveness and migratory capacity. These cells showed reduced E-cadherin and increased N-cadherin and Vimentin levels, all markers of epithelial–mesenchymal transition (EMT). Primary enteric glial cell CM inhibited the proliferation of PDAC cells but preserved their viability, upregulated transcription factor Snail , and increased their resistance to gemcitabine. The conditioned medium generated from the IMS32 SCs produced comparable results. Conclusion Our data suggest that glial cells can increase the metastatic potential of PDAC cells by increasing their migratory capacity and inducing epithelial-to-mesenchymal transition, a re-programming that many solid tumors use to undergo metastasis. Glial cell-conditioned medium also increased the chemoresistance of PDAC cells. These findings may have implications for future therapeutic strategies, such as targeting glial cell-derived factor signaling in PDAC. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-023-05133-y.

CITATION EXPORT

Balbina García-Reyes, Ivan Kuzmanov, Reiner Schneider et al.. Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition. Journal of Cancer Research and Clinical Oncology. (2023). https://doi.org/10.1007/s00432-023-05133-y

AUTHORS

7 · 2 CENTRES

Balbina García-Reyes, Ivan Kuzmanov, Reiner Schneider, Bianca Schneiker, Patrik Efferz, Jörg C. Kalff, Sven Wehner

1https://ror.org/01xnwqx93grid.15090.3d0000 0000 8786 803XDepartment of Surgery, Medical Faculty, University Hospital Bonn, Bonn, Germany
2https://ror.org/01xnwqx93grid.15090.3d0000 0000 8786 803XMildred Scheel School of Oncology, Aachen Bonn Cologne Düsseldorf (MSSO ABCD), Medical Faculty, University Hospital Bonn, Bonn, Germany