title: The role of stromal cancer-associated fibroblasts in pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer generally refractory to conventional treatments. Cancer-associated fibroblasts (CAFs) are cellular components of the desmoplastic stroma characteristic to the tumor that contributes to this treatment resistance. Various markers for CAFs have been explored including palladin and CD146 that have prognostic and functional roles in the pathobiology of PDAC. Mechanisms of CAF-tumor cell interaction have been described including exosomal transfer and paracrine signaling mediated by cytokines such as GM-CSF and IL-6. The role of downstream signaling pathways including JAK/STAT, mTOR, sonic hedge hog (SHH), and NFkB have also been shown to play an important function in PDAC-CAF cross talk. The role of autophagy and other metabolic effects on each cell type within the tumor have also been proposed to play roles in facilitating CAF secretory function and enhancing tumor growth in a low-glucose microenvironment. Targeting the stroma has gained interest with multiple preclinical and clinical trials targeting SHH, JAK2, and methods of either exploiting the secretory capability of CAFs to enhance drug delivery or inhibiting it to prevent its influence on cancer cell chemoresistance. This review summarizes the most recent progress made in understanding stromal formation; its contribution to tumor proliferation, invasion, and metastasis; its role in chemoresistance; and potential therapeutic strategies on the horizon.
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Dagny
authors.initials: D
authors.lastname: von Ahrens
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
authors.forename: Tushar D
authors.initials: TD
authors.lastname: Bhagat
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Nagrath
authors.affiliation: The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.affiliation: Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA. averma@aecom.yu.edu.
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
mesh_terms: D000072645:Cancer-Associated Fibroblasts / Q000473:pathology*; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D017154:Stromal Cells; D059016:Tumor Microenvironment
keywords: Adenocarcinoma; Cancer-associated fibroblast; Pancreas; Stroma; Tumor microenvironment