Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma Journal Article
| Authors: | Lou, E.; Fujisawa, S.; Morozov, A.; Barlas, A.; Romin, Y.; Dogan, Y.; Gholami, S.; Moreira, A. L.; Manova-Todorova, K.; Moore, M. A. S. |
| Article Title: | Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma |
| Abstract: | Tunneling nanotubes are long, non-adherent F-actin-based cytoplasmic extensions which connect proximal or distant cells and facilitate intercellular transfer. The identification of nanotubes has been limited to cell lines, and their role in cancer remains unclear. We detected tunneling nanotubes in mesothelioma cell lines and primary human mesothelioma cells. Using a low serum, hyperglycemic, acidic growth medium, we stimulated nanotube formation and bidirectional transfer of vesicles, proteins, and mitochondria between cells. Notably, nanotubes developed between malignant cells or between normal mesothelial cells, but not between malignant and normal cells. Immunofluorescent staining revealed their actin-based assembly and structure. Metformin and an mTor inhibitor, Everolimus, effectively suppressed nanotube formation. Confocal microscopy with 3-dimensional reconstructions of sectioned surgical specimens demonstrated for the first time the presence of nanotubes in human mesothelioma and lung adenocarcinoma tumor specimens. We provide the first evidence of tunneling nanotubes in human primary tumors and cancer cells and propose that these structures play an important role in cancer cell pathogenesis and invasion. © 2012 Lou et al. |
| Keywords: | controlled study; human cell; electron microscopy; metabolism; microscopy, electron; actin; disease association; confocal microscopy; microscopy, confocal; protein assembly; intracellular transport; cancer cell culture; cell line, tumor; physiology; cancer invasion; fluorescent antibody technique; chemistry; lung adenocarcinoma; three dimensional imaging; tumor cell line; protein transport; pleura mesothelioma; mesothelioma; pleura tumor; molecular interaction; immunofluorescence test; lung carcinogenesis; image processing, computer-assisted; image processing; cell communication; metformin; everolimus; ultrastructure; pleural neoplasms; biological transport; golgi complex; transport at the cellular level; nanotubes; nanotube; time lapse imaging; time-lapse imaging |
| Journal Title: | PLoS ONE |
| Volume: | 7 |
| Issue: | 3 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2012-01-01 |
| Start Page: | e33093 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0033093 |
| PROVIDER: | scopus |
| PMCID: | PMC3302868 |
| PUBMED: | 22427958 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 April 2012" - "Source: Scopus" |
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