Oncotarget

Research Papers:

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

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

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Oncotarget. 2017; 8:15539-15552. https://doi.org/10.18632/oncotarget.14695

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Abstract

Jinjin Lu1, Xiufen Zheng2, Fan Li1, Yang Yu3, Zhong Chen1, Zheng Liu1, Zhihua Wang1, Hua Xu1, Weimin Yang1

1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China

2Department of Pathology, Department of Oncology, Department of Surgery, Western University, Lawson Health Research Institute, London, Ontario, N6A 5A5, Canada

3Department of Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P. R. China

Correspondence to:

Fan Li, email: [email protected]

Keywords: tunneling nanotubes, mitochondria, bladder cancer, cell invasion, cell connection

Received: July 06, 2016     Accepted: December 27, 2016     Published: January 17, 2017

ABSTRACT

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.


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