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.
| Original language | English (US) |
|---|---|
| Article number | e33093 |
| Journal | PLoS One |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 9 2012 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma. / Lou, Emil; Fujisawa, Sho; Morozov, Alexei; Barlas, Afsar; Romin, Yevgeniy; Dogan, Yildirim; Gholami, Sepideh; Moreira, André L.; Manova-Todorova, Katia; Moore, Malcolm A.S.
In: PLoS One, Vol. 7, No. 3, e33093, 09.03.2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma
AU - Lou, Emil
AU - Fujisawa, Sho
AU - Morozov, Alexei
AU - Barlas, Afsar
AU - Romin, Yevgeniy
AU - Dogan, Yildirim
AU - Gholami, Sepideh
AU - Moreira, André L.
AU - Manova-Todorova, Katia
AU - Moore, Malcolm A.S.
PY - 2012/3/9
Y1 - 2012/3/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84857926403&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857926403&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0033093
DO - 10.1371/journal.pone.0033093
M3 - Article
C2 - 22427958
AN - SCOPUS:84857926403
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 3
M1 - e33093
ER -