Patient-derived ovarian cancer explants: preserved viability and histopathological features in long-term agitation-based cultures
| Autor: | Rita Mendes, Teresa F. Mendes, Marta Teixeira, Vítor E. Santo, Catarina Brito, Sofia Abreu, Fernanda Silva, Erwin R. Boghaert, Ana Félix |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer microenvironment
Adult Cell type Time Factors Cell Survival Cell Culture Techniques lcsh:Medicine Antineoplastic Agents Drug resistance Biology Article Immune system Lymphocytes Tumor-Infiltrating Ovarian cancer Ovarian carcinoma medicine Tumor Cells Cultured Chemotherapy Humans Cancer models lcsh:Science Aged Aged 80 and over Ovarian Neoplasms Multidisciplinary lcsh:R Cancer Epithelial Cells Fibroblasts Middle Aged medicine.disease Cancer therapeutic resistance Ki-67 Antigen Apoptosis Cancer research Female lcsh:Q Explant culture |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Ovarian carcinoma (OvC) remains a major therapeutic challenge due to its propensity to develop resistance after an initial response to chemotherapy. Interactions of tumour cells with the surrounding microenvironment play a role in tumour survival, invasion capacity and drug resistance. Cancer models that retain tissue architecture and tumour microenvironment components are therefore essential to understand drug response and resistance mechanisms. Herein, our goal was to develop a long-term OvC patient-derived explant (OvC-PDE) culture strategy in which architecture and cell type heterogeneity of the original tumour would be retained. Samples from 25 patients with distinct OvC types and one with a benign tumour, were cultured for 30 days in agitation-based culture systems with 100% success rate. OvC-PDE cultures retained the original tumour architecture and main cellular components: epithelial cells, fibroblasts and immune cells. Epithelial cells kept their original levels of proliferation and apoptosis. Moreover, the major extracellular components, such as collagen-I and -IV, were retained in explants. OvC-PDE cultures were exposed to standard-of-care chemotherapeutics agents for 2 weeks, attesting the ability of the platform for drug assays employing cyclic drug exposure regimens. We established an OvC-PDE dynamic culture in which tumour architecture and cell type heterogeneity were preserved for the different OvC types, replicating features of the original tumour and compatible with long-term drug exposure for drug efficacy and resistance studies. |
| Databáze: | OpenAIRE |
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