- These unique conduits have attracted increasing interest as an under-recognized mechanism of cell-to-cell communication and transfer of cellular contents.
The loss and transfer of cellular components in nanovesicles is consistent with the loss of protein expression by Per that has been reported by Fu et al. They showed that Per decreased components of the PI3K/mTOR/Akt pathway, such as Akt, raptor, rictor, mtor, p70S6K and 4EBP-1.
- Furthermore, TNTs have been shown to be involved in the spread of pathogens, and transfer of aberrant cellular proteins responsible for disease, such as prions and misfolded huntingtin., In addition to this wide range of functions, studies performed during the last decade have revealed a high level of heterogeneity in TNT morphology and structure, even within the same cell line.
Recently characterized cellular bridges - cytonemes and tunneling nanotubes (TNTs) - facilitate transfer of cellular signals and components, even pathogens, over hundreds of microns representing the longest direct connections between cells in vitro and in vivo [4] [9].
Our recent study of tunneling nanotubes in human malignant pleural mesothelioma and lung adenocarcinomas demonstrated efficient transfer of cellular contents, including proteins, Golgi vesicles, and mitochondria, between cells derived from several well-established cancer cell lines.
Exosomes are well-known mediators of communication between cells and could be responsible for the transfer of cellular communication between irradiated and unirradiated (bystander) cells.
Cellular bridges, the longest direct connections between cells, facilitate transfer of cellular signals and components over hundreds of microns in vitro and in vivo.
Live-cell imaging of lysosomes (Figure 3B) and the presence of a Golgi apparatus structural protein within vesicle-like structures in EP bridges (Figure 3C and Figure S7A) also supports the notion that these structures mediate transfer of cellular components between cells; however, these observations are not definitive proof that EP bridges transfer cellular cargo from one cell to another.
We have recently shown that intercellular transfer of cellular cargo such as proteins, Golgi vesicles, and mitochondria takes place between malignant mesothelioma cells via TnTs.
Clinically applied modalities of cancer immunotherapy include the adoptive transfer of cellular immune effectors by means of allogeneic stem cell transplantation and donor lymphocyte therapy, monoclonal antibodies with direct and indirect cytotoxic mechanisms, and active immunotherapy with cellular and acellular vaccines.
A recent FDA report explains that the agency was previously concerned about the inadvertent transfer of cellular constituents, such as chromosomes, to the offspring.
