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Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition
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 secreti...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590291/ https://www.ncbi.nlm.nih.gov/pubmed/37572121 http://dx.doi.org/10.1007/s00432-023-05133-y |
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author | García-Reyes, Balbina Kuzmanov, Ivan Schneider, Reiner Schneiker, Bianca Efferz, Patrik Kalff, Jörg C. Wehner, Sven |
author_facet | García-Reyes, Balbina Kuzmanov, Ivan Schneider, Reiner Schneiker, Bianca Efferz, Patrik Kalff, Jörg C. Wehner, Sven |
author_sort | García-Reyes, Balbina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10590291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-105902912023-10-23 Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition García-Reyes, Balbina Kuzmanov, Ivan Schneider, Reiner Schneiker, Bianca Efferz, Patrik Kalff, Jörg C. Wehner, Sven J Cancer Res Clin Oncol Research 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. Springer Berlin Heidelberg 2023-08-12 2023 /pmc/articles/PMC10590291/ /pubmed/37572121 http://dx.doi.org/10.1007/s00432-023-05133-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research García-Reyes, Balbina Kuzmanov, Ivan Schneider, Reiner Schneiker, Bianca Efferz, Patrik Kalff, Jörg C. Wehner, Sven Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition |
title | Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition |
title_full | Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition |
title_fullStr | Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition |
title_full_unstemmed | Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition |
title_short | Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition |
title_sort | glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590291/ https://www.ncbi.nlm.nih.gov/pubmed/37572121 http://dx.doi.org/10.1007/s00432-023-05133-y |
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