التفاصيل البيبلوغرافية
| العنوان: |
Chemoresistance is mediated by ovarian cancer leader cells in vitro |
| المؤلفون: |
Nazanin Karimnia, Amy L. Wilson, Emma Green, Amelia Matthews, Thomas W. Jobling, Magdalena Plebanski, Maree Bilandzic, Andrew N. Stephens |
| المصدر: |
Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-13 (2021) |
| بيانات النشر: |
BMC, 2021. |
| سنة النشر: |
2021 |
| المجموعة: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: |
Ovarian Cancer, Leader cells, Keratin-14, Chemo-resistance, Recurrence, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: |
Abstract 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. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1756-9966 |
| Relation: |
https://doaj.org/toc/1756-9966 |
| DOI: |
10.1186/s13046-021-02086-3 |
| URL الوصول: |
https://doaj.org/article/3a4f2b92608642eb89cf00da7af241cc |
| رقم الانضمام: |
edsdoj.3a4f2b92608642eb89cf00da7af241cc |
| قاعدة البيانات: |
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