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

https://www.ncbi.nlm.nih.gov/pubmed/28107184

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

In cell culture, cells have been observed to create long, thin, protrusions to connect to other cells and transfer material, including entire organelles such as mitochondria. These protrusions are called tunneling nanotubes (TNTs). In this study, the authors co-culture two kinds of urothelial bladder cancer cells: T24 (highly invasive) and RT4 (less invasive) cells. The authors observed the formation of TNTs between the two cell types and mitochondrial exchange between the cell types.

The authors found that the RT4 cells became more motile after intercellular mitochondria trafficking from T24 cells (RT4-Mito-T24) by around a factor of 2 relative to RT4 cells. Xenograft tumours from RT4-Mito-T24 cells were also around twice as large as T24 cells after ~30 days of growth.

This shows that transfer of material from a highly invasive cell type to a less invasive cell type results in increased invasive ability. It suggests that mitochondrial content may be the causal variable in determining invasive ability in this system.

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Thoughts: This study adds to a growing body of evidence that mitochondrial content contributes to determining metastatic potential of cancer cells. What is it about these mitochondria that causes the increase in invasiveness? Are there other factors which are transferred through the TNTs? Is mitochondrial transfer necessary, or indeed sufficient, to see these effects? Interesting to note that the nuclear background of these cell types are presumably not the same -- to what extent can the nuclei be different between these cell types to observe the increase in invasiveness?