Academic Journal
Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells
| العنوان: | Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells |
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| المؤلفون: | Yakinthi Chrisochoidou, Rajat Roy, Pooyeh Farahmand, Guadalupe Gonzalez, Jennifer Doig, Lukas Krasny, Ella F. Rimmer, Anne E Willis, Marion MacFarlane, Paul H. Huang, Neil O. Carragher, Alison F. Munro, Daniel J. Murphy, Kirill Veselkov, Michael J. Seckl, Miriam F. Moffatt, William O. C. Cookson, Olivier E. Pardo |
| المصدر: | Cell Death and Disease, Vol 14, Iss 11, Pp 1-20 (2023) |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2023 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Cytology, QH573-671 |
| الوصف: | Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking. Here, using co-cultures of patient-derived mesothelioma cell lines and lung fibroblasts, we demonstrate that fibroblast activation is a self-propagated process producing a fibrotic extracellular matrix (ECM) and triggering drug resistance in mesothelioma cells. Following characterisation of mesothelioma cells/fibroblasts signalling crosstalk, we identify several FDA-approved targeted therapies as far more potent than standard-of-care Cisplatin/Pemetrexed in ECM-embedded co-culture spheroid models. In particular, the SRC family kinase inhibitor, Saracatinib, extends overall survival well beyond standard-of-care in a mesothelioma genetically-engineered mouse model. In short, we lay the foundation for the rational design of novel therapeutic strategies targeting mesothelioma/fibroblast communication for the treatment of mesothelioma patients. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2041-4889 |
| Relation: | https://doi.org/10.1038/s41419-023-06240-x; https://doaj.org/toc/2041-4889; https://doaj.org/article/aaf6d7ac3e1a4d1b86de96ee85ac0b92 |
| DOI: | 10.1038/s41419-023-06240-x |
| الاتاحة: | https://doi.org/10.1038/s41419-023-06240-x https://doaj.org/article/aaf6d7ac3e1a4d1b86de96ee85ac0b92 |
| رقم الانضمام: | edsbas.A5B7BD2A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20414889 |
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| DOI: | 10.1038/s41419-023-06240-x |