ArticleCancers2019
Role of c-MET Inhibitors in Overcoming Drug Resistance in Spheroid Models of Primary Human Pancreatic Cancer and Stellate Cells.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 75 citations in OpenAlex.
- Dynamic evaluation of the glycolytic determinants LDH-A and GLUT-1 enhances prognostic significance and their inhibition affects the growth of mesothelioma spheroids.Molecular metabolism · 2026Article
- Ferroptosis- and stemness inhibition-mediated therapeutic potency of ferrous oxide nanoparticles-diethyldithiocarbamate using a co-spheroid 3D model of pancreatic cancer.Journal of gastroenterology · 2025Article
- MicroRNA-130b Suppresses Malignant Behaviours and Inhibits the Activation of the PI3K/Akt Signaling Pathway by Targeting MET in Pancreatic Cancer.Biochemical genetics · 2025Article
- Mapping Tumor-Stroma-ECM Interactions in Spatially Advanced 3D Models of Pancreatic Cancer.ACS applied materials & interfaces · 2025Article
- Construction and application of pancreatic exocrine organoid and spheroid for drug screening and precision medicine.Frontiers in cell and developmental biology · 2025Review
- A promising breakthrough in pancreatic cancer research: The potential of spheroids as 3D models.BioImpacts : BI · 2025Review
- Article
- A prognostic binary classifier comprised of five critical mRNAs stratified pancreatic cancer patients following resection.Heliyon · 2024Article
- Synergistic eradicating impact of 5-fluouracil with FeO nanoparticles-diethyldithiocarbamate in colon cancer spheroids.Nanomedicine (London, England) · 2024Article
- Integrated single-cell and bulk RNA sequencing in pancreatic cancer identifies disulfidptosis-associated molecular subtypes and prognostic signature.Scientific reports · 2023Article
- Heterotypic tumor spheroids: a platform for nanomedicine evaluation.Journal of nanobiotechnology · 2023Review
- HGF/c-Met pathway inhibition combined with chemotherapy increases cytotoxic T-cell infiltration and inhibits pancreatic tumour growth and metastasis.Cancer letters · 2023Article
- Article
- Emerging roles of 3D-culture systems in tackling tumor drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2023Review
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- Article
- Reversible Monoacylglycerol Lipase Inhibitors: Discovery of a New Class of Benzylpiperidine Derivatives.Journal of medicinal chemistry · 2022Article
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Epithelial and Mesenchymal Features of Pancreatic Ductal Adenocarcinoma Cell Lines in Two- and Three-Dimensional Cultures.Journal of personalized medicine · 2022Review
- Study of the anticancer effect of new quinazolinone hydrazine derivatives as receptor tyrosine kinase inhibitors.Frontiers in chemistry · 2022Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 4 countries.
Funding
Abstract
Pancreatic stellate cells (PSCs) are a key component of tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) and contribute to drug resistance. c-MET receptor tyrosine kinase activation plays an important role in tumorigenesis in different cancers including PDAC. In this study, effects of PSC conditioned medium (PCM) on c-MET phosphorylation (by immunocytochemistry enzyme-linked immunosorbent assay (ELISA)) and drug response (by sulforhodamine B assay) were investigated in five primary PDAC cells. In novel 3D-spheroid co-cultures of cyan fluorescence protein (CFP)-firefly luciferase (Fluc)-expressing primary human PDAC cells and green fluorescence protein (GFP)-expressing immortalized PSCs, PDAC cell growth and chemosensitivity were examined by luciferase assay, while spheroids' architecture was evaluated by confocal microscopy. The highest phospho-c-MET expression was detected in PDAC5 and its subclone sorted for "stage specific embryonic antigen-4" (PDAC5 (SSEA4)). PCM of cells pre-incubated with PDAC conditioned medium, containing increased hepatocyte growth factor (HGF) levels, made PDAC cells significantly more resistant to gemcitabine, but not to c-MET inhibitors. Hetero-spheroids containing both PSCs and PDAC5 (SSEA4) cells were more resistant to gemcitabine compared to PDAC5 (SSEA4) homo-spheroids. However, c-MET inhibitors (tivantinib, PHA-665752 and crizotinib) were equally effective in both spheroid models. Experiments with primary human PSCs confirmed the main findings. In conclusion, we developed spheroid models to evaluate PSC-PDAC reciprocal interaction, unraveling c-MET inhibition as an important therapeutic option against drug resistant PDAC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.