Tunneling nanotubes promote intercellular mitochondria transfer followed by increased invasiveness in bladder cancer cells

Intercellular transfer of organelles via tunneling nanotubes (TNTs) is a novel means of cell-to-cell communication. Here we demonstrate the existence of TNTs between co-cultured RT4 and T24 bladder cancer cells using light microscopy, fluorescence imaging, and scanning electron microscopy (SEM). Spontaneous unidirectional transfer of mitochondria from T24 to RT4 cells was detected using fluorescence imaging and flow cytometry. The distribution of mitochondria migrated from T24 cells was in good agreement with the original mitochondria in RT4 cells, which may imply mitochondrial fusion. We detected cytoskeleton reconstruction in RT4-Mito-T24 cells by observing F-actin redistribution. Akt, mTOR, and their downstream mediators were activated and increased. The resultant increase in the invasiveness of bladder cancer cells was detected in vitro and in vivo. These data indicate that TNTs promote intercellular mitochondrial transfer between heterogeneous cells, followed by an increase in the invasiveness of bladder cancer cells.

Oncotarget. 2017 Jan 17 [Epub ahead of print]

Jinjin Lu, Xiufen Zheng, Fan Li, Yang Yu, Zhong Chen, Zheng Liu, Zhihua Wang, Hua Xu, Weimin Yang

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China., Department of Pathology, Department of Oncology, Department of Surgery, Western University, Lawson Health Research Institute, London, Ontario, N6A 5A5, Canada., Department of Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China.