We are analyzing https://link.springer.com/article/10.1186/s13046-022-02519-7.

Title:
Patient-specific modeling of stroma-mediated chemoresistance of pancreatic cancer using a three-dimensional organoid-fibroblast co-culture system | Journal of Experimental & Clinical Cancer Research
Description:
Background Cancer-associated fibroblasts (CAFs) are considered to play a fundamental role in pancreatic ductal adenocarcinoma (PDAC) progression and chemoresistance. Patient-derived organoids have demonstrated great potential as tumor avatars for drug response prediction in PDAC, yet they disregard the influence of stromal components on chemosensitivity. Methods We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs to investigate the effect of the fibroblastic compartment on sensitivity to gemcitabine, 5-fluorouracil and paclitaxel treatments using an image-based drug assay. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-stroma interaction. Results Upon co-culture with CAFs, we observed increased proliferation and reduced chemotherapy-induced cell death of PDAC organoids. Single-cell RNA sequencing data evidenced induction of a pro-inflammatory phenotype in CAFs in co-cultures. Organoids showed increased expression of genes associated with epithelial-to-mesenchymal transition (EMT) in co-cultures and several potential receptor-ligand interactions related to EMT were identified, supporting a key role of CAF-driven induction of EMT in PDAC chemoresistance. Conclusions Our results demonstrate the potential of personalized PDAC co-cultures models not only for drug response profiling but also for unraveling the molecular mechanisms involved in the chemoresistance-supporting role of the tumor stroma.
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Keywords {🔍}

cells, cafs, pdac, cancer, coculture, article, tumor, organoids, pancreatic, organoid, fig, cell, google, scholar, drug, genes, cas, cocultures, caf, expression, proliferation, data, supplementary, analysis, emt, interactions, cluster, gemcitabine, models, response, identified, gene, clusters, chemoresistance, stromal, potential, fibroblasts, adenocarcinoma, patientderived, performed, transcriptional, related, culture, heidelberg, line, samples, clinical, observed, increased, death,

Topics {✒️}

multi-subunit ligand–receptor complexes cross-species single-cell analysis tumor-stroma cross-talk analyses anti-apoptosis/pro-survival pathways single-cell rna sequencing image-based drug assay fine-needle biopsies patient-specific tumor microenvironment patient-derived xenografts shows single-cell sequencing libraries inferring cell–cell communication patient-derived organoid pharmacotyping receptor-ligand interactions related tumor-stroma interactions occurring single cells/small aggregates european genome-phenome archive image-based drug testing predicted receptor-ligand interaction 1 mg/ml collagenase iv fine-tuning pdo/caf potential ligand-receptor interactions potential receptor-ligand interactions caf-tumor cell doublets patient-derived pdac organoids solange le blanc patient-derived organoid line cd44-stromal ligand network article download pdf pancreatic ductal adenocarcinoma fluorescence microscopy-based imaging full size image emt-related interactions occurred patient-specific modeling patient-matched pdac organoids tumor tissue modeling differentiating drug responses patient-derived xenografts caf marker α-sma ligand-receptor interactions [32] patient-derived organoids pancreatic adenocarcinoma organoids patient-specific heterogeneity 1 μg/ml propidium iodide stroma-derived insulin single cell analyses scrna-seq analyses identified tumor-stroma interaction individual emt-related genes promising therapeutic approach privacy choices/manage cookies

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      headline:Patient-specific modeling of stroma-mediated chemoresistance of pancreatic cancer using a three-dimensional organoid-fibroblast co-culture system
      description:Cancer-associated fibroblasts (CAFs) are considered to play a fundamental role in pancreatic ductal adenocarcinoma (PDAC) progression and chemoresistance. Patient-derived organoids have demonstrated great potential as tumor avatars for drug response prediction in PDAC, yet they disregard the influence of stromal components on chemosensitivity. We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs to investigate the effect of the fibroblastic compartment on sensitivity to gemcitabine, 5-fluorouracil and paclitaxel treatments using an image-based drug assay. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-stroma interaction. Upon co-culture with CAFs, we observed increased proliferation and reduced chemotherapy-induced cell death of PDAC organoids. Single-cell RNA sequencing data evidenced induction of a pro-inflammatory phenotype in CAFs in co-cultures. Organoids showed increased expression of genes associated with epithelial-to-mesenchymal transition (EMT) in co-cultures and several potential receptor-ligand interactions related to EMT were identified, supporting a key role of CAF-driven induction of EMT in PDAC chemoresistance. Our results demonstrate the potential of personalized PDAC co-cultures models not only for drug response profiling but also for unraveling the molecular mechanisms involved in the chemoresistance-supporting role of the tumor stroma.
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            name:University Hospital Heidelberg
            address:
               name:European Pancreas Center, Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
            name:NCT partner site Heidelberg, a clinical-translational cancer research partnership between University Hospital Heidelberg and DKFZ
            address:
               name:NCT partner site Heidelberg, a clinical-translational cancer research partnership between University Hospital Heidelberg and DKFZ, Heidelberg, Germany
               type:PostalAddress
            type:Organization
            name:Medical University of Vienna
            address:
               name:Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:European Pancreas Center, Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
      name:European Pancreas Center, Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
      name:Division of Molecular Oncology of Gastrointestinal Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany
      name:NCT partner site Heidelberg, a clinical-translational cancer research partnership between University Hospital Heidelberg and DKFZ, Heidelberg, Germany
      name:Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
      name:Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Digital Health Center, Berlin, Germany
      name:Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany
      name:Present Address: Merck Healthcare KGaA, Global Research, Darmstadt, Germany
      name:European Pancreas Center, Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
      name:European Pancreas Center, Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
      name:European Pancreas Center, Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
      name:Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Digital Health Center, Berlin, Germany
      name:Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany
      name:Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Digital Health Center, Berlin, Germany
      name:Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany
      name:European Pancreas Center, Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany
      name:NCT partner site Heidelberg, a clinical-translational cancer research partnership between University Hospital Heidelberg and DKFZ, Heidelberg, Germany
      name:Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria

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