Pancreatic Cancer: The Role of Pancreatic Stellate Cells in Tumor Progression

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2011-03, Vol.10 (6), p.673-681
• Main Authors: Dunér, Siri, Lindman, Jacob Lopatko, Ansari, Daniel, Gundewar, Chinmay, Andersson, Roland
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - metabolism; Carcinoma, Pancreatic Ductal - blood supply; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - secondary; Clinical Medicine; Desmoplasia; Disease Progression; Endocrinology & Metabolism; Extracellular Matrix - metabolism; Gastroenterology and Hepatology; Humans; Kirurgi; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Neoplasm Invasiveness; Neovascularization, Pathologic; Pancreatic cancer; Pancreatic cancer, treatment; Pancreatic Neoplasms - blood supply; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pancreatic Stellate Cells - metabolism; Pancreatic Stellate Cells - pathology; Review; Signal Transduction; Stellate cells; Surgery
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1159/000320711

Abstract Pancreatic ductal adenocarcinoma is an aggressive and highly lethal disease frequently characterized by a dense stromal or desmoplastic response. Accumulating evidence exists that tumor desmoplasia plays a central role in disease progression and that e.g. activated pancreatic stellate cells (PSCs) are responsible for the excess matrix production. The mechanisms underlying the tumor versus stroma interplay are complex. Pancreatic cancer cells release mitogenic and fibrogenic stimulants, such as transforming growth factor β1 platelet-derived growth factor (PDGF), sonic hedgehog, galectin 3, endothelin 1 and serine protease inhibitor nexin 2, all of which may promote the activated PSC phenotype. Stellate cells in turn secrete various factors, including PDGF, stromal-derived factor 1, epidermal growth factor, insulin-like growth factor 1, fibroblast growth factor, secreted protein acidic and rich in cysteine, matrix metalloproteinases, small leucine-rich proteoglycans, periostin and collagen type I that mediate effects on tumor growth, invasion, metastasis and resistance to chemotherapy. This review intends to shed light on the mechanisms by which PSCs in the stroma influence pancreatic cancer development. The increased understanding of this interaction will be of potential value in designing new modalities of targeted therapy.