Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids

类有机物 胶质母细胞瘤 癌症干细胞 癌症研究 干细胞 放射治疗 体内 线粒体 癌细胞 癌症 生物 医学 化学 病理 细胞生物学 内科学 遗传学
作者
Giulia Pinto,Inés Sáenz‐de‐Santa‐María,Patricia Chastagner,Émeline Perthame,Caroline Delmas,Christine Toulas,Elizabeth Moyal-Jonathan-Cohen,Christel Brou,Chiara Zurzolo
出处
期刊:Biochemical Journal [Portland Press]
卷期号:478 (1): 21-39 被引量:109
标识
DOI:10.1042/bcj20200710
摘要

Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor's features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observed in vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking.

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