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

Journal of Translational Medicine

Arash Rafii⁵  Frank Le Foll⁴  Shahin Rafii⁵  Ludovic Galas¹  Massoud Mirshahi³  Arthur Jacob²  Nadine Abu-Kaoud²  Mahtab Maleki²  Pegah Ghiabi²  Hamda Al Thawadi²  Bella S Guerrouahen⁵  Jennifer Pasquier⁵ 

[1] Primacen Cellular Imaging Platform, University of Rouen, Mont-Saint-Aignan 76821, France;Stem Cell and Microenvironment Laboratory, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha PO: 24144, Qatar;UMRS 872 INSERM, Université Pierre et Marie Curie-Paris 6 and Université Paris Descartes, Equipe 18, Centre de Recherche des Cordeliers, 15 rue de l’Ecole de Medecine, Paris Cedex 06 75270, France;Laboratory of Ecotoxicology, University of Le Havre, Le Havre 76058, France;Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, USA

关键词: Chemoresistance;    Cancer cells;    Endothelial cells;    Intercellular transfer;    Tunneling nanotubes;   

Others  :  827691
DOI  :  10.1186/1479-5876-11-94

 received in 2013-02-05, accepted in 2013-03-27,  发布年份 2013

【 摘 要 】

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 chemoresistance. Our results illustrate the perfusion-independent role of the endothelium by showing a direct endothelial to cancer cell mitochondrial exchange associated to phenotypic modulation. This supports another role of the endothelium in the constitution of the metastatic niche.

【 授权许可】

   
2013 Pasquier et al.; licensee BioMed Central Ltd.

【 图 表 】

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