Chemoresistance is mediated by ovarian cancer leader cells in vitro
| العنوان: | Chemoresistance is mediated by ovarian cancer leader cells in vitro |
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| المؤلفون: | Maree Bilandzic, Magdalena Plebanski, Amelia Matthews, Andrew N. Stephens, Nazanin Karimnia, Emma Green, Tom Jobling, Amy L. Wilson |
| المصدر: | Journal of Experimental & Clinical Cancer Research : CR Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-13 (2021) |
| بيانات النشر: | BioMed Central, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | DNA Replication, Cancer Research, Cell division, Green Fluorescent Proteins, Cell, Antineoplastic Agents, Apoptosis, Caspase 3, Biology, Flow cytometry, Chemo-resistance, Live cell imaging, Recurrence, Cell Line, Tumor, medicine, Leader cells, Humans, Clustered Regularly Interspaced Short Palindromic Repeats, RC254-282, Cell Proliferation, Ovarian Neoplasms, medicine.diagnostic_test, Research, Keratin-14, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Ovarian Cancer, medicine.anatomical_structure, Oncology, Drug Resistance, Neoplasm, Cancer cell, Cancer research, Female, Cisplatin, Ovarian cancer |
| الوصف: | Background Leader cells are a subset of cancer cells that coordinate the complex cell-cell and cell-matrix interactions required for ovarian cancer migration, invasion, tumour deposition and are negatively associated with progression-free survival and response to therapy. Emerging evidence suggests leader cells may be enriched in response to chemotherapy, underlying disease recurrence following treatment. Methods CRISPR was used to insert a bicistronic T2A-GFP cassette under the native KRT14 (leader cell) promoter. 2D and 3D drug screens were completed in the presence of chemotherapies used in ovarian cancer management. Leader cell; proliferative (Ki67); and apoptotic status (Cleaved Caspase 3) were defined by live cell imaging and flow cytometry. Quantitative real-time PCR defined “stemness” profiles. Proliferation was assessed on the xCELLigence real time cell analyser. Statistical Analysis was performed using unpaired non-parametric t-tests or one-way ANOVA and Tukey’s multiple comparison post hoc. Results Leader cells represent a transcriptionally plastic subpopulation of ovarian cancer cells that arise independently of cell division or DNA replication, and exhibit a “stemness” profile that does not correlate with epithelial-to-mesenchymal transition. Chemotherapeutics increased apoptosis-resistant leader cells in vitro, who retained motility and expressed known chemo-resistance markers including ALDH1, Twist and CD44v6. Functional impairment of leader cells restored chemosensitivity, with leader cell-deficient lines failing to recover following chemotherapeutic intervention. Conclusions Our data demonstrate that ovarian cancer leader cells are resistant to a diverse array of chemotherapeutic agents, and are likely to play a critical role in the recurrence of chemo-resistant disease as drivers of poor treatment outcomes. |
| اللغة: | English |
| تدمد: | 1756-9966 0392-9078 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd4eec91bb2c97304d1c4316bf994112 http://europepmc.org/articles/PMC8408956 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cd4eec91bb2c97304d1c4316bf994112 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17569966 03929078 |
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