cells Review Pancreatic Fibroblast Heterogeneity: From Development to Cancer 1, 2, 2,3 Paloma E. Garcia y, Michael K. Scales y, Benjamin L. Allen and Marina Pasca di Magliano 2,3,4,* 1 Program in Molecular and Cellular Pathology, University of Michigan Medical School, University of Michigan, Ann Arbor, MI 48105, USA;
[email protected] 2 Department of Cell and Developmental Biology, University of Michigan Medical School, University of Michigan, Ann Arbor, MI 48109, USA;
[email protected] (M.K.S.);
[email protected] (B.L.A.) 3 Rogel Cancer Center, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA 4 Department of Surgery, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA * Correspondence:
[email protected]; Tel.: +1-734-276-7104 Authors contributed equally to this work. y Received: 22 October 2020; Accepted: 10 November 2020; Published: 12 November 2020 Abstract: Pancreatic ductal adenocarcinoma (PDA) is characterized by an extensive fibroinflammatory microenvironment that accumulates from the onset of disease progression. Cancer-associated fibroblasts (CAFs) are a prominent cellular component of the stroma, but their role during carcinogenesis remains controversial, with both tumor-supporting and tumor-restraining functions reported in different studies. One explanation for these contradictory findings is the heterogeneous nature of the fibroblast populations, and the different roles each subset might play in carcinogenesis. Here, we review the current literature on the origin and function of pancreatic fibroblasts, from the developing organ to the healthy adult pancreas, and throughout the initiation and progression of PDA. We also discuss clinical approaches to targeting fibroblasts in PDA. Keywords: fibroblasts; pancreas; cancer-associated fibroblasts; pancreas development; pancreatic cancer; tumor microenvironment; hedgehog; transforming growth factor Beta 1.