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Cancer-Associated Fibroblasts’ Functional Heterogeneity in Pancreatic Ductal Adenocarcinoma

Department of Pathology and Microbiology, University of Nebraska Medical Center, 985845 UNMC, Omaha, NE 68198-5845, USA
Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital-Dammam, Dammam 31444, Saudi Arabia
Author to whom correspondence should be addressed.
Cancers 2019, 11(3), 290;
Received: 11 February 2019 / Revised: 22 February 2019 / Accepted: 26 February 2019 / Published: 1 March 2019
(This article belongs to the Special Issue Advances in Pancreatic Cancer Research)
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths in the USA. Desmoplasia and inflammation are two major hallmarks of PDAC. Desmoplasia, composed of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), and infiltrating immune and endothelial cells, acts as a biophysical barrier to hinder chemotherapy and actively contributes to tumor progression and metastasis. CAFs represent a multifunctional subset of PDAC microenvironment and contribute to tumor initiation and progression through ECM deposition and remodeling, as well as the secretion of paracrine factors. Attempts to resolve desmoplasia by targeting CAFs can render an adverse outcome, which is likely due to CAFs heterogeneity. Recent reports describe subsets of CAFs that assume more secretory functions, in addition to the typical myofibroblast phenotype. Here, we review the literature and describe the relationship between CAFs and inflammation and the role of the secretory-CAFs in PDAC. View Full-Text
Keywords: pancreatic cancer; PDAC; cancer-associated fibroblast; myofibroblast; inflammation; IL-6; CXCL8; TGF-β pancreatic cancer; PDAC; cancer-associated fibroblast; myofibroblast; inflammation; IL-6; CXCL8; TGF-β
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Awaji, M.; Singh, R.K. Cancer-Associated Fibroblasts’ Functional Heterogeneity in Pancreatic Ductal Adenocarcinoma. Cancers 2019, 11, 290.

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