Robert Beauchamp
Principal Investigator
Last active: 10/31/2018

Fibrogenesis in pancreatic cancer is a dynamic process regulated by macrophage-stellate cell interaction.

Shi C, Washington MK, Chaturvedi R, Drosos Y, Revetta FL, Weaver CJ, Buzhardt E, Yull FE, Blackwell TS, Sosa-Pineda B, Whitehead RH, Beauchamp RD, Wilson KT, Means AL
Lab Invest. 2014 94 (4): 409-21

PMID: 24535260 · PMCID: PMC3992484 · DOI:10.1038/labinvest.2014.10

Pancreatic cancer occurs in the setting of a profound fibrotic microenvironment that often dwarfs the actual tumor. Although pancreatic fibrosis has been well studied in chronic pancreatitis, its development in pancreatic cancer is much less well understood. This article describes the dynamic remodeling that occurs from pancreatic precursors (pancreatic intraepithelial neoplasias (PanINs)) to pancreatic ductal adenocarcinoma, highlighting similarities and differences between benign and malignant disease. Although collagen matrix is a commonality throughout this process, early stage PanINs are virtually free of periostin while late stage PanIN and pancreatic cancer are surrounded by an increasing abundance of this extracellular matrix protein. Myofibroblasts also become increasingly abundant during progression from PanIN to cancer. From the earliest stages of fibrogenesis, macrophages are associated with this ongoing process. In vitro co-culture indicates there is cross-regulation between macrophages and pancreatic stellate cells (PaSCs), precursors to at least some of the fibrotic cell populations. When quiescent PaSCs were co-cultured with macrophage cell lines, the stellate cells became activated and the macrophages increased cytokine production. In summary, fibrosis in pancreatic cancer involves a complex interplay of cells and matrices that regulate not only the tumor epithelium but the composition of the microenvironment itself.

MeSH Terms (13)

Animals Carcinoma, Pancreatic Ductal Cell Line Disease Models, Animal Disease Progression Fibrosis Macrophages Metaplasia Mice Pancreas Pancreatic Neoplasms Pancreatic Stellate Cells Receptor Cross-Talk

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