Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance

作者：Jennifer Pasquier, Bella Samia Guerrouahen, Hamda Al. Thawadi, Pegah Ghiabi, Mahtab Maleki, Nadine Abu-Kaoud, Arthur Jacob, Massoud Mirshahi, Ludovic Galas, Shahin Rafii, Frank Le Foll, Arash Rafii · 发表于：Journal of Translational Medicine · 年份：2013 · DOI：10.1186/1479-5876-11-94 · 被引用次数：514 · 研究领域：Extracellular vesicles in disease、Nanoplatforms for cancer theranostics、MicroRNA in disease regulation

Our vision of cancer has changed during the past decades. Indeed tumors are now perceived as complex entities where tumoral and stromal components interact closely. Among the different elements of tumor stroma the cellular component play a primordial role. Bone Marrow derived mesenchymal cells (MSCs) are attracted to tumor sites and support tumor growth. Endothelial cells (ECs) play a major role in angiogenesis. While the literature documents many aspects of the cross talk between stromal and cancer cells, the role of direct hetero-cellular contact is not clearly established. Recently, Tunneling nanotubes (TnTs) have been shown to support cell-to-cell transfers of plasma membrane components, cytosolic molecules and organelles within cell lines. Herein, we have investigated the formation of heterocellular TnTs between stromal (MSCs and ECs) and cancer cells. We demonstrate that TnTs occur between different cancer cells, stromal cells and cancer-stromal cell lines. We showed that TnTs-like structure occurred in 3D anchorage independent spheroids and also in tumor explant cultures. In our culture condition, TnTs formation occurred after large membrane adhesion. We showed that intercellular transfers of cytoplasmic content occurred similarly between cancer cells and MSCs or ECs, but we highlighted that the exchange of mitochondria occurred preferentially between endothelial cells and cancer cells. We illustrated that the cancer cells acquiring mitochondria displayed chemoresistan...