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Mesothelioma-Associated Fibroblasts Modulate the Response of Mesothelioma Patient-Derived Organoids to Chemotherapy via Interleukin-6.
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- المؤلفون: Cioce, Mario1,2 (AUTHOR) ; Gatti, Veronica1 (AUTHOR); Napolitano, Fabiana3 (AUTHOR); Giorgiano, Noemi Maria4 (AUTHOR); Marra, Andrea1,2 (AUTHOR); Portella, Giuseppe3 (AUTHOR); Fiorelli, Alfonso4 (AUTHOR); Pentimalli, Francesca5 (AUTHOR); Fazio, Vito Michele1,2 (AUTHOR)
- المصدر:
International Journal of Molecular Sciences. May2024, Vol. 25 Issue 10, p5355. 13p.
- الموضوع:
- معلومة اضافية
- نبذة مختصرة :
Malignant pleural mesothelioma (MPM) remains an incurable disease. This is partly due to the lack of experimental models that fully recapitulate the complexity and heterogeneity of MPM, a major challenge for therapeutic management of the disease. In addition, the contribution of the MPM microenvironment is relevant for the adaptive response to therapy. We established mesothelioma patient-derived organoid (mPDO) cultures from MPM pleural effusions and tested their response to pemetrexed and cisplatin. We aimed to evaluate the contribution of mesothelioma-associated fibroblasts (MAFs) to the response to pemetrexed and cisplatin (P+C). Organoid cultures were obtained from eight MPM patients using specific growth media and conditions to expand pleural effusion-derived cells. Flow cytometry was used to verify the similarity of the organoid cultures to the original samples. MAFs were isolated and co-cultured with mPDOs, and the addition of MAFs reduced the sensitivity of mPDOs to P+C. Organoid formation and expression of cancer stem cell markers such as ABCG2, NANOG, and CD44 were altered by conditioned media from treated MAFs. We identified IL-6 as the major contributor to the attenuated response to chemotherapy. IL-6 secretion by MAFs is correlated with increased resistance of mPDOs to pemetrexed and cisplatin. [ABSTRACT FROM AUTHOR]
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