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Cellular Heterogeneity of Pancreatic Stellate Cells, Mesenchymal Stem Cells, and Cancer-Associated Fibroblasts in Pancreatic Cancer

Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center Halle, 06120 Halle, Germany
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Author to whom correspondence should be addressed.
Cancers 2020, 12(12), 3770; https://doi.org/10.3390/cancers12123770
Received: 10 November 2020 / Revised: 10 December 2020 / Accepted: 11 December 2020 / Published: 15 December 2020
(This article belongs to the Special Issue Recent Advances in Pancreatic Ductal Adenocarcinoma)
Cancer-associated fibroblasts, which are derived from several cell types such as pancreatic stellate cells or mesenchymal stem cells, play a major role in the progression and drug resistance of pancreatic cancer. Targeting cancer-associated fibroblasts can, therefore, be a promising therapeutic strategy. However, several studies show that deletion of cancer-associated fibroblasts may also have tumor-promoting effects. These contrasting observations suggest that cancer-associated fibroblasts exhibit functional heterogeneity in pancreatic cancer.
Pancreatic cancer is projected to become the second deadliest cancer by 2030 in the United States, and the overall five-year survival rate stands still at around 9%. The stroma compartment can make up more than 90% of the pancreatic tumor mass, contributing to the hypoxic tumor microenvironment. The dense stroma with extracellular matrix proteins can be a physical and metabolic barrier reducing therapeutic efficacy. Cancer-associated fibroblasts are a source of extracellular matrix proteins. Therefore, targeting these cells, or extracellular matrix proteins, have been considered as therapeutic strategies. However, several studies show that deletion of cancer-associated fibroblasts may have tumor-promoting effects. Cancer-associated fibroblasts are derived from a variety of different cell types, such as pancreatic stellate cells and mesenchymal stem cells, and constitute a diverse cell population consisting of several functionally heterogeneous subtypes. Several subtypes of cancer-associated fibroblasts exhibit a tumor-restraining function. This review article summarizes recent findings regarding origin and functional heterogeneity of tumor-promoting as well as tumor-restraining cancer-associated fibroblasts. A better understanding of cancer-associated fibroblast heterogeneity could provide more specific and personalized therapies for pancreatic cancer patients in the future. View Full-Text
Keywords: pancreatic cancer; cancer-associated fibroblasts; pancreatic stellate cells; mesenchymal stem cells; cancer-restraining cancer-associated fibroblast; cellular heterogeneity pancreatic cancer; cancer-associated fibroblasts; pancreatic stellate cells; mesenchymal stem cells; cancer-restraining cancer-associated fibroblast; cellular heterogeneity
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MDPI and ACS Style

Sunami, Y.; Häußler, J.; Kleeff, J. Cellular Heterogeneity of Pancreatic Stellate Cells, Mesenchymal Stem Cells, and Cancer-Associated Fibroblasts in Pancreatic Cancer. Cancers 2020, 12, 3770. https://doi.org/10.3390/cancers12123770

AMA Style

Sunami Y, Häußler J, Kleeff J. Cellular Heterogeneity of Pancreatic Stellate Cells, Mesenchymal Stem Cells, and Cancer-Associated Fibroblasts in Pancreatic Cancer. Cancers. 2020; 12(12):3770. https://doi.org/10.3390/cancers12123770

Chicago/Turabian Style

Sunami, Yoshiaki; Häußler, Johanna; Kleeff, Jörg. 2020. "Cellular Heterogeneity of Pancreatic Stellate Cells, Mesenchymal Stem Cells, and Cancer-Associated Fibroblasts in Pancreatic Cancer" Cancers 12, no. 12: 3770. https://doi.org/10.3390/cancers12123770

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