Selected SummaryHomeostatic Restoration of Desmoplastic Stroma Rather Than Its Ablation Slows Pancreatic Cancer Progression
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Using detailed methods, transcriptome analyses, and orthotopic and genetically engineered mouse models, Sherman et al elegantly show that modulation, rather than ablation, of the desmoplastic stroma, in which PSC regain a more physiologic secretome, offers an attractive therapeutic strategy in pancreatic cancer. The imbalance of desmoplastic stroma driving aggressive tumor behavior has been demonstrated recently (J Pathol 2013;230:107–117). This approach, of reprogramming the pancreatic tumor
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2024, European Journal of PharmacologyThe roles of collagens and fibroblasts in cancer
2023, Biochemistry of Collagens, Laminins and Elastin: Structure, Function and Biomarkers, Third EditionCancer-associated fibroblasts: Origin, function, imaging, and therapeutic targeting
2022, Advanced Drug Delivery ReviewsCitation Excerpt :However, clinical trials with GEM did not show satisfactory results [381,382]. Few preclinical studies reported that depleting CAF may not enhance tumor control and increase the risk of losing critical stromal elements required for tissue homeostasis, thereby leading to tumor progression [253,383,384]. This suggests that the role of desmoplasia is very context-dependent, and the patient benefit might require re-educating CAF to become more normal.
Disruption of pancreatic stellate cell myofibroblast phenotype promotes pancreatic tumor invasion
2022, Cell ReportsCitation Excerpt :In pancreatic ductal adenocarcinoma (PDAC), resident PSCs become activated in response to tumor-derived paracrine signals, such as transforming growth factor-β (TGF-β), sonic hedgehog (Shh), and platelet-derived growth factor (PDGF), resulting in desmoplastic, hypovascular tumors, which respond poorly to therapy. The reciprocal interaction between malignant PDAC cells and PSCs has therefore attracted increasing attention clinically, and identifying targets to modify PSC function is a priority (Froeling and Kocher, 2015; Kocher et al., 2020). We reported recently that the Rho effector kinase, protein kinase N2 (PKN2), but not PKN1 or PKN3, plays a critical role during developmental expansion of the embryonic mesoderm (Quetier et al., 2016).
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2020, Annals of Diagnostic PathologyCitation Excerpt :Patients with pancreatic ductal adenocarcinoma (PDAC) lack pancreatic and biliary secretions, which leads to a deficiency of fat-soluble vitamins, such as vitamin A (retinol). Pancreatic stellate cells (PSCs) lose their retinol stores to trans-differentiate into activated (myo-)fibroblasts, also known as cancer-associated fibroblasts (CAFs), which in turn are responsible for the desmoplastic reaction in PDAC [1]. Chronic pancreatitis as well as other pancreatic disorders also affect PSC behaviour.