Pancreatic cancer: the role of pancreatic stellate cells in tumor progression.
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 β(1), 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. and IAP.
Department of Surgery, Clinical Sciences Lund, Lund University and Lund University Hospital, Lund, Sweden.
Siri
S
Dunér
Jacob
J
Lopatko Lindman
Daniel
D
Ansari
Chinmay
C
Gundewar
Roland
R
Andersson
D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
D014408:Biomarkers, Tumor