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 AS (2012) Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma. PLoS One, 7 (3). e33093. ISSN 1932-6203

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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.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders > cancer > cancer types > mesothelioma
CSHL Authors:	Gholami, Sepideh
Communities:	CSHL labs > Gholami Lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2012
Date Deposited:	05 Oct 2023 20:30
Last Modified:	05 Oct 2023 20:30
PMCID:	PMC3302868
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41167

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