ArticleInternational journal of molecular sciences2020
Extracellular Matrix Composition Modulates the Responsiveness of Differentiated and Stem Pancreatic Cancer Cells to Lipophilic Derivate of Gemcitabine.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Acidosis Drives Vasculogenic Mimicry in PDAC CSCs via Na+/H+ Exchanger Isoform 1 (NHE1) and Calcium Entry.Cells · 2026Article
- The molecular puzzle of recurrent implantation failure: integrating genetic, epigenetic, and immune mechanisms for precision reproductive medicine.Journal of assisted reproduction and genetics · 2026Review
- Extracellular pH and NHE1 Regulate Ductal Branching Morphogenesis in Organotypic Cultures of Human Pancreatic Duct Epithelial Cells.Journal of cellular physiology · 2026Article
- Expression and clinical significance of CD155, FGL1, Galectin-9, and PD‑L1 in breast cancer with neoadjuvant chemotherapy.Medical oncology (Northwood, London, England) · 2025Article
- Article
- Design, Synthesis, and Antitumor Evaluation of an Opioid Growth Factor Bioconjugate Targeting Pancreatic Ductal Adenocarcinoma.Pharmaceutics · 2024Article
- Gemcitabine-Vitamin E Prodrug-Loaded Micelles for Pancreatic Cancer Therapy.Pharmaceutics · 2024Article
- Article
- ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells.International journal of molecular sciences · 2023Article
- Glucocorticoid-induced microRNA-378 signaling mediates the progression of pancreatic cancer by enhancing autophagy.Cell death & disease · 2022Article
- Cancer Associated Fibroblast (CAF) Regulation of PDAC Parenchymal (CPC) and CSC Phenotypes Is Modulated by ECM Composition.Cancers · 2022Article
- 3-Bromo-Isoxazoline Derivatives Inhibit GAPDH Enzyme in PDAC Cells Triggering Autophagy and Apoptotic Cell Death.Cancers · 2022Article
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Article
- Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Gemcitabine (GEM) is used as the gold standard drug in PDAC treatment. However, due to its poor efficacy, it remains urgent to identify novel strategies to overcome resistance issues. In this context, an intense stroma reaction and the presence of cancer stem cells (CSCs) have been shown to influence PDAC aggressiveness, metastatic potential, and chemoresistance.
methodsWe used three-dimensional (3D) organotypic cultures grown on an extracellular matrix composed of Matrigel or collagen I to test the effect of the new potential therapeutic prodrug 4-(N)-stearoyl-GEM, called C18GEM. We analyzed C18GEM cytotoxic activity, intracellular uptake, apoptosis, necrosis, and autophagy induction in both Panc1 cell line (P) and their derived CSCs.
resultsPDAC CSCs show higher sensitivity to C18GEM treatment when cultured in both two-dimensional (2D) and 3D conditions, especially on collagen I, in comparison to GEM. The intracellular uptake mechanisms of C18GEM are mainly due to membrane nucleoside transporters' expression and fatty acid translocase CD36 in Panc1 P cells and to clathrin-mediated endocytosis and CD36 in Panc1 CSCs. Furthermore, C18GEM induces an increase in cell death compared to GEM in both cell lines grown on 2D and 3D cultures. Finally, C18GEM stimulated protective autophagy in Panc1 P and CSCs cultured on 3D conditions.
conclusionWe propose C18GEM together with autophagy inhibitors as a valid alternative therapeutic approach in PDAC treatment.
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