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Mechanisms of Disease: chronic inflammation and cancer in the pancreas—a potential role for pancreatic stellate cells?

Abstract

Late diagnosis and ineffective therapeutic options mean that pancreatic ductal adenocarcinoma (PDA) is one of the most lethal forms of human cancer. The identification of genetic alterations facilitated the launch of the Pancreatic Intraepithelial Neoplasm nomenclature, a standardized classification system for pancreatic duct lesions, but the factors that contribute to the development of such lesions and their progression to high-grade neoplasia remain obscure. Age, smoking, obesity and diabetes confer increased risk of PDA, and the presence of chronic pancreatitis is a consistent risk factor for pancreatic cancer. It is hypothesized that chronic inflammation generates a microenvironment that contributes to malignant transformation in the pancreas, as is known to occur in other organs. Pancreatic stellate cells (PSCs) are the main mediator of fibrogenesis during chronic pancreatitis, but their contribution to the development of PDA has not been elucidated. Data now suggest that PSCs might assume a linking role in inflammation-associated carcinogenesis through their ability to communicate with inflammatory cells, acinar cells, and pancreatic cancer cells in a complicated network of interactions. In this Review, the role of PSCs in the process of inflammation-associated carcinogenesis is discussed and new potential treatment options evaluated.

Key Points

  • The pancreatic stellate cell (PSC) is a recently identified cell population in the pancreas

  • The PSC's ability to produce extracellular matrix proteins, growth factors, cytokines and chemokines means that it has an important role in chronic inflammatory processes of the pancreas

  • Although the role of PSCs in chronic pancreatitis has been defined over the past 5 years, the role of PSCs in pancreatic cancer is not yet understood

  • Data now indicate that PSCs have a crucial role in inflammation-associated cancer of the pancreas; analyzing the role of PSCs in pancreatic cancer might, therefore, broaden the horizon of understanding PDA and open up new therapeutic or diagnostic options

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Figure 1: Genetic and morphologic progression model of pancreatic adenocarcinoma
Figure 2: The interaction of various cell types in inflammation and carcinogenesis

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Correspondence to Roland M Schmid.

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Algül, H., Treiber, M., Lesina, M. et al. Mechanisms of Disease: chronic inflammation and cancer in the pancreas—a potential role for pancreatic stellate cells?. Nat Rev Gastroenterol Hepatol 4, 454–462 (2007). https://doi.org/10.1038/ncpgasthep0881

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