Pancreatic cancer is a particularly aggressive tumor, distinguished by the presence of a prominent collagenous stroma and desmoplasia that envelops the tumor cells. Pancreatic stellate cell (PSC) contributes to the formation of a dense fibrotic stroma and has been demonstrated to facilitate tumor progression. As the significance of PSCs is increasingly revealed, more explorations are focused on the complex molecular mechanisms and tumor-stromal crosstalk in order to guide potential therapeutic approaches through deactivating or reprogramming PSCs. Nevertheless, significant challenges persist in translating preclinical discoveries into clinical applications. In this review, we expect to offer a comprehensive overview of the latest molecular advancements in PSCs, along with new insights into the clinical therapeutic strategies targeting PSCs.
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http://dx.doi.org/10.1002/ijc.35326 | DOI Listing |
Int J Cancer
January 2025
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Center, Peking University Cancer Hospital and Institute, Beijing, China.
Pancreatic cancer is a particularly aggressive tumor, distinguished by the presence of a prominent collagenous stroma and desmoplasia that envelops the tumor cells. Pancreatic stellate cell (PSC) contributes to the formation of a dense fibrotic stroma and has been demonstrated to facilitate tumor progression. As the significance of PSCs is increasingly revealed, more explorations are focused on the complex molecular mechanisms and tumor-stromal crosstalk in order to guide potential therapeutic approaches through deactivating or reprogramming PSCs.
View Article and Find Full Text PDFCell Physiol Biochem
January 2025
UR-UPJV 4667, UFR Sciences, Université de Picardie Jules Verne, Amiens, France,
Quiescent pancreatic stellate cells (PSCs) represent only a very low proportion of the pancreatic tissue, but their activation leads to stroma remodeling and fibrosis associated with pathologies such as chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC). PSC activation can be induced by various stresses, including acidosis, growth factors (PDGF, TGFβ), hypoxia, high pressure, or intercellular communication with pancreatic cancer cells. Activated PSC targeting represents a promising therapeutic strategy, but little is known regarding the molecular mechanisms underlying the activation of PSCs.
View Article and Find Full Text PDFNat Commun
January 2025
Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions.
View Article and Find Full Text PDFHepatol Commun
November 2024
Department of Medicine, University of California, San Diego, La Jolla, California, USA.
Background: Liver fibrosis is caused by chronic toxic or cholestatic liver injury. Fibrosis results from the recruitment of myeloid cells into the injured liver, the release of inflammatory and fibrogenic cytokines, and the activation of myofibroblasts, which secrete extracellular matrix, mostly collagen type I. Hepatic myofibroblasts originate from liver-resident mesenchymal cells, including HSCs and bone marrow-derived CD45+ collagen type I+ expressing fibrocytes.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Transplantation Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin Province 130061, China. Electronic address:
Chronic hepatitis B virus (HBV) infection is a major risk factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite advances in understanding HBV-related liver diseases, effective therapeutic strategies remain limited. Macrophage migration inhibitory factor (MIF) has been implicated in various inflammatory and fibrotic conditions, but its role in HBV-induced liver fibrosis has not been fully explored.
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