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
Notes: --- - "Export Date: 2 April 2012" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Andre L Moreira
    176 Moreira
  2. Emil Lou
    11 Lou
  3. Sepideh Gholami
    30 Gholami
  4. Afsar Barlas
    26 Barlas
  5. Yildirim Dogan
    13 Dogan
  6. Malcolm A S Moore
    476 Moore
  7. Yevgeniy Romin
    16 Romin