ArticleAmerican journal of respiratory cell and molecular biology2005
A novel in vitro model of human mesothelioma for studying tumor biology and apoptotic resistance.
Article in American journal of respiratory cell and molecular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 73 citations in OpenAlex.
- Simulated Microgravity-Induced Alterations in PDAC Cells: A Potential Role for Trichostatin A in Restoring Cellular Phenotype.International journal of molecular sciences · 2025Article
- Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review.ACS pharmacology & translational science · 2024Review
- Quantum Dots Mediated Imaging and Phototherapy in Cancer Spheroid Models: State of the Art and Perspectives.Pharmaceutics · 2022Review
- Organoids as a Model for Precision Medicine in Malignant Pleural Mesothelioma: Where Are We Today?Cancers · 2022Review
- Review
- Artificial Tumor Microenvironments in Neuroblastoma.Cancers · 2021Review
- Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma - A Review.Frontiers in oncology · 2021Review
- 3D Tumor Spheroid Models for In Vitro Therapeutic Screening of Nanoparticles.Advances in experimental medicine and biology · 2021Article
- The Biology of Malignant Mesothelioma and the Relevance of Preclinical Models.Frontiers in oncology · 2020Review
- Improved Anticancer Effect of Recombinant Protein izTRAIL Combined with Sorafenib and Peptide iRGD.International journal of molecular sciences · 2019Article
- HSP90 inhibition alters the chemotherapy-driven rearrangement of the oncogenic secretome.Oncogene · 2018Article
- Personalized in vitro cancer models to predict therapeutic response: Challenges and a framework for improvement.Pharmacology & therapeutics · 2016Review
- Autophagy initiation correlates with the autophagic flux in 3D models of mesothelioma and with patient outcome.Autophagy · 2016Article
- Decoy receptors block TRAIL sensitivity at a supracellular level: the role of stromal cells in controlling tumour TRAIL sensitivity.Oncogene · 2016Article
- Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors.Cell death & disease · 2015Article
- Spherical cancer models in tumor biology.Neoplasia (New York, N.Y.) · 2015Review
- Extracellular signal-regulated kinase 5 and cyclic AMP response element binding protein are novel pathways inhibited by vandetanib (ZD6474) and doxorubicin in mesotheliomas.American journal of respiratory cell and molecular biology · 2014Article
- Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-miR-34a-c-Met axis.Cancer research · 2014Article
- Cyclooxygenase-2 inhibitor is a robust enhancer of anticancer agents against hepatocellular carcinoma multicellular spheroids.OncoTargets and therapy · 2014Article
- Synergistic inhibition of mesothelioma cell growth by the combination of clofarabine and resveratrol involves Nrf2 downregulation.BMB reports · 2012Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Like many tumors, malignant mesothelioma exhibits significant chemoresistance and resistance to apoptosis in vivo that is not seen in current in vitro models. To study the mechanisms of this multicellular resistance, biologically relevant in vitro models are necessary. Therefore, we characterized and tested human mesothelioma tissue grown in vitro as tumor fragment spheroids. After 5-10 d in culture, fragments from each of 15 human mesothelioma tumors rounded into spheroids. The tumor fragment spheroids maintained multiple characteristics of the original tumors for up to 3 mo including the presence of viable mesothelioma cells, macrophages, and a collagen-rich stroma. In 14-d-old spheroids, mesothelioma cells showed the same proliferation rate and expression of a death receptor, DR5, as in the original tumor. To determine responses to treatment, we treated tumor fragment spheroids grown from three separate tumors with agents, TNF-related apoptosis-inducing ligand (TRAIL) plus cycloheximide, that induced near total apoptosis in three human mesothelioma cell lines (M28, REN, MS-1) grown as monolayers (94 +/- 6% apoptosis; mean +/- SEM). Compared with mesothelioma cells in monolayers, mesothelioma cells in the spheroids were resistant to TRAIL plus cycloheximide (32 +/- 4% apoptosis; mean +/- SEM). Apoptotic resistance of mesothelioma cells was significantly reduced by inhibiting either the PI3K/Akt pathway with LY294002 (47 +/- 6% apoptosis) or the mTOR pathway with rapamycin (50 +/- 17% apoptosis). We conclude that human mesothelioma can be maintained in vitro in a biologically relevant model that exhibits apoptotic resistance, thereby permitting study of its tumor biology and of novel approaches to therapy.
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