Abstract
Pancreatic stellate cells play a pivotal role in the development of pancreatic fibrosis. A wide variety of external stimuli can cause PSC activation accompanied by metabolic changes, which alters the tissue microenvironment by producing extracellular matrix proteins, cytokines, growth factors, and other mediators. Several metabolites aggravate fibrosis and inflammation by acting as key activating factors for PSCs. In other words, PSCs sense systemic metabolic changes. The detrimental effects of PSC activation on normal pancreatic cells, especially islet cells, further complicate metabolic imbalance through the dysregulation of glucose metabolism. PSC activation promotes cancer by altering the metabolism in pancreatic cancer cells, which collaborate with PSCs to efficiently adapt to environmental changes, promoting their growth and survival. This collaboration also contributes to the acquisition of chemoresistance. PSCs sequester chemotherapeutic agents and produce competing molecules as additional resistance mechanisms. The application of these metabolic targets for novel therapeutic strategies is currently being explored. This mini-review summarizes the role of PSCs in metabolic regulation of normal and cancerous cells.
Highlights
Pancreatic stellate cells (PSCs) play pivotal roles in the development of fibrosis through the production of extracellular matrix (ECM) proteins, growth factors, and cytokines (Erkan et al, 2012)
PSCs contribute to the pathogenesis of pancreatitis and pancreatic cancer by modifying the cellular microenvironment (Masamune and Shimosegawa, 2015), thereby contributing to the development of pancreatic fibrosis, which creates hypoxia, poor blood supply, and mechanical barriers
These structural and environmental changes have a substantial impact on the cellular functions of normal pancreatic cells, leading to tissue damage, and exocrine and endocrine insufficiency
Summary
Pancreatic stellate cells (PSCs) play pivotal roles in the development of fibrosis through the production of extracellular matrix (ECM) proteins, growth factors, and cytokines (Erkan et al, 2012). PSCs contribute to the pathogenesis of pancreatitis and pancreatic cancer by modifying the cellular microenvironment (Masamune and Shimosegawa, 2015), thereby contributing to the development of pancreatic fibrosis, which creates hypoxia, poor blood supply, and mechanical barriers. These structural and environmental changes have a substantial impact on the cellular functions of normal pancreatic cells, leading to tissue damage, and exocrine and endocrine insufficiency. Recent studies have identified metabolic alterations in PSCs, normal pancreatic cells, and pancreatic cancer cells that affect cellular functions. We discuss the possibilities for therapeutic applications based on cancer-promoting PSC activation
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