ArticleJournal of experimental & clinical cancer research : CR2015
Associations of chemo- and radio-resistant phenotypes with the gap junction, adhesion and extracellular matrix in a three-dimensional culture model of soft sarcoma.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
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- Feasibility and barriers to rapid establishment of patient-derived primary osteosarcoma cell lines in clinical management.iScience · 2024Review
- 3D Models of Sarcomas: The Next-generation Tool for Personalized Medicine.Phenomics (Cham, Switzerland) · 2024Review
- Article
- The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.Biology · 2023Review
- Establishment of a three‑dimensional triculture model on the novel AXTEX‑4D™ platform.Oncology reports · 2023Article
- Review
- Extracellular matrix stiffness mediates radiosensitivity in a 3D nasopharyngeal carcinoma model.Cancer cell international · 2022Article
- Super-Long SERS Active Single Silver Nanowires for Molecular Imaging in 2D and 3D Cell Culture Models.Biosensors · 2022Article
- 3D Multicellular Tumor Spheroids in a Microfluidic Droplet System for Investigation of Drug Resistance.Polymers · 2022Article
- NELL1 Regulates the Matrisome to Promote Osteosarcoma Progression.Cancer research · 2022Article
- Osteosarcoma tumor microenvironment: the key for the successful development of biologically relevant 3D in vitro models.In vitro models · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThree-dimensional (3D) culture models are considered to recapitulate the cell microenvironment in solid tumors, including the extracellular matrix (ECM), cell-cell interactions, and signal transduction. These functions are highly correlated with cellular behaviors and contribute to resistances against chemo- and radio-therapies. However, the biochemical effects and mechanisms remain unknown in soft sarcoma. Therefore, we developed an in vitro 3D model of sarcoma to analyze the reasons of the chemo- and radio-resistance in therapies.
methodsFour soft sarcoma cell lines, HT1080, RD, SW872, and human osteosarcoma cell line 1 (HOSS1), a cell line established from a patient-derived xenograft, were applied to 3D culture and treated with growth factors in methylcellulose-containing medium. Spheroids were examined morphologically and by western blotting, RT-qPCR, and immunofluorescence staining to analyze cell adhesion, gap junctions, ECM genes, and related factors. Proliferation and colony formation assays were performed to assess chemo- and radio-resistances between 3D and two-dimensional (2D) cell cultures. Annexin V and Propidium Iodide staining was used to detect early apoptotic sarcoma cells treated with Doxorubicin, Gemcitabine, and Docetaxel in the 3D model.
resultsThe four soft sarcoma cell lines formed spheres in vitro by culture in modified condition medium. Compared with 2D cell culture, expression of ECM genes and proteins, including COL1A1, LOX, SED1, FN1, and LAMA4, was significantly increased in 3D culture. Analysis of cadherin and gap junction molecules showed significant changes in the gene and protein expression profiles under 3D conditions. These changes affected cell-cell communication and were mainly associated with biological processes such as cell proliferation and apoptosis related to chemo- and radio-resistances.
conclusionsOur findings revealed significant differences between 3D and 2D cell culture systems, and indicated that cellular responsiveness to external stress such as radiation and chemotherapeutics is influenced by differential expression of genes and proteins involved in regulation of the ECM, cell adhesion, and gap junction signaling.
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