| Autor: |
Barceló, C., Sisó, P., de la Rosa, I., Megino-Luque, C., Navaridas, R., Maiques, O., Urdanibia, I., Eritja, N., Soria, X., Potrony, M., Calbet-Llopart, N., Puig, S., Matías-Guiu, X., Martí, R. M., Macià, A. |
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| Zdroj: |
British Journal of Cancer; Oct2022, Vol. 127 Issue 6, p1142-1152, 11p |
| Abstrakt: |
Background: Disseminated BRAFV600E melanoma responds to BRAF inhibitors (BRAFi) but easily develops resistance with poor prognosis. Secretome plays a pivotal role during tumour progression causing profound effects on therapeutic efficacy. Secreted M-CSF is involved in both cytotoxicity suppression and tumour progression in melanoma. We aimed to analyse the M-CSF contribution in resistant metastatic melanoma to BRAF-targeted therapies.Methods: Conditioned media from melanoma cells were analysed by citoarray. Viability and migration/invasion assays were performed with paired melanoma cells and tumour growth in xenografted SCID mice. We evaluated the impact of M-CSF plasma levels with clinical prognosis from 35 metastatic BRAFV600E-mutant melanoma patients.Results: BRAFi-resistant melanoma cells secretome is rich in pro-tumour cytokines. M-CSF secretion is essential to induce a Vemurafenib-resistant phenotype in melanoma cells. Further, we demonstrated that M-CSF mAb in combination with Vemurafenib and autophagy blockers synergistically induce apoptosis, impair migration and reduce tumour growth in BRAFi-resistant melanoma cells. Interestingly, lower M-CSF plasma levels are associated with better prognosis in metastatic melanoma patients.Conclusions: Secreted M-CSF induces a BRAFi-resistant phenotype and means worse prognosis in BRAFV600E metastatic melanoma patients. These results identify secreted M-CSF as a promising therapeutic target toward BRAFi-resistant melanomas. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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