Abstract
Pancreatic cancer is associated with highly malignant tumors and poor prognosis due to strong therapeutic resistance. Accumulating evidence shows that activated pancreatic stellate cells (PSC) play an important role in the malignant progression of pancreatic cancer. In recent years, the rapid development of single-cell sequencing technology has facilitated the analysis of PSC population heterogeneity, allowing for the elucidation of the relationship between different subsets of cells with tumor development and therapeutic resistance. Researchers have identified two spatially separated, functionally complementary, and reversible subtypes, namely myofibroblastic and inflammatory PSC. Myofibroblastic PSC produce large amounts of pro-fibroproliferative collagen fibers, whereas inflammatory PSC express large amounts of inflammatory cytokines. These distinct cell subtypes cooperate to create a microenvironment suitable for cancer cell survival. Therefore, further understanding of the differentiation of PSC and their distinct functions will provide insight into more effective treatment options for pancreatic cancer patients.
Highlights
Pancreatic cancer is among the most deadly forms of cancer, with a mortality-to-incidence ratio of 0.82 in 2020 and a 5 year survival rate of about 9% (Mizrahi et al, 2020)
Cancer-associated fibroblasts (CAF) that are induced by cancer cells are mesenchymal-derived cells and play an active role in promoting pancreatic cancer progression
Pancreatic cancer has a high degree of desmoplasia, which is characterized by the differentiation of pancreatic stellate cells (PSC) into myofibroblastic PSC and overexpression of extracellular matrix (ECM) proteins (Incio et al, 2016)
Summary
Pancreatic cancer is among the most deadly forms of cancer, with a mortality-to-incidence ratio of 0.82 in 2020 and a 5 year survival rate of about 9% (Mizrahi et al, 2020). Interstitial cells, especially pancreatic stellate cells (PSC), play an important role in the malignant progression and treatment resistance observed in pancreatic cancer patients. PSC promote the fibrosis and inflammatory response of the tumor microenvironment by producing a large number of collagen fibers, exosomes, and soluble factors, which provide the basis for the proliferation, migration, and immune escape of pancreatic cancer cells (Wang et al, 2020), (Wang et al, 2017). PSC promote EMT in pancreatic cancer cells by secreting exosomal microRNA-21 (Ma et al, 2020). Myofibroblastic PSC, characterized by elevated a-smooth muscle actin (α-SMA) expression, produce large amounts of profibroproliferative collagen fibers, whereas inflammatory PSC express large amounts of inflammatory cytokines These two subtypes of PSC have been shown to operate synergistically to promote the progression of pancreatic cancer (Öhlund et al, 2017). We propose a more effective approach to manage treatment resistance in pancreatic cancer, at the level of PSC heterogeneity
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