Pancreatic stellate cell: Pandora's box for pancreatic disease biology

Abstract

Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotype via an autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Several pathways (e.g., JAK-STAT, Smad, Wnt signaling, Hedgehog etc.), transcription factors and miRNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma.

Dissecting cell type-specific metabolism in pancreatic ductal adenocarcinoma

“…Another approach that has been used to determine which cell type(s) within the tumor contribute to a metabolic activity is isolating distinct cell populations and studying them in culture (Dalin et al, 2019;Francescone et al, 2018;Linares et al, 2017;Sousa et al, 2016;Valencia et al, 2014;Yang et al, 2016). Pancreatic stellate cells (PSCs) are a type of resident fibroblast in the pancreas which can become activated during tumorigenesis and can impact the tumor microenvironment (Bynigeri et al, 2017;Dunér et al, 2011). When PDAC cells or PSCs alone are cultured in the presence of 13 Cglucose in vitro, PSCs exhibit similar or higher M+3 TCA cycle metabolite labeling than cancer cells ( Figure 2D-E), even though the fibroblast cell population exhibited lower PC expression in tumors (Figure 2A-B).…”

Структурна Трансформація Протокової Системи Підшлункової Залози У Хворих На Хронічний Панкреатит

“…В дальнейшем это приводит к образованию бел-ковых пробок панкреатических протоков вследствие повышенной секреции белков ПЖ, которые являются очагами кальцификации и приводят к образованию конкрементов в протоковой системе ПЖ [5]. В резуль-тате поражается эпителий протоков, который образует слепки и закупоривает протоки, тем самым вызывая воспалительные изменения и потерю функционирую-щей паренхимы ПЖ вследствие фиброза [4,6,7].…”

Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic β‐cell mass and function

“…Quiescent PSCs are characterized by the presence of intracellular fat droplets, desmin and glial fibrillary acidic protein, but the absence of α‐SMA. When activated, PSCs are transformed into the myofibroblast‐like phenotype characterized by the disappearance of intracellular fat droplets and the expression of α‐SMA. The expression of glial fibrillary acidic protein is specific to PSCs in the pancreas, and the presence of lipid droplets in the cytoplasm defines the quiescent phenotype of PSCs.…”