Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma

Our plain-English summary of Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma, by E. Lou, S. Fujisawa, A. Morozov, et al (PloS One, 2012).

The study

• Authors: E. Lou, S. Fujisawa, A. Morozov, A. Barlas, Y. Romin, Y. Dogan, S. Gholami, A.L. Moreira, K. Manova-Todorova, M.A. Moore
• Journal: PloS One
• Published: 2012;7(3):e33093
• Cited by: 331 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory study did not examine asbestos exposure. It looked at tunneling nanotubes, thin tube-like connections between cells, in mesothelioma. The authors studied mesothelioma cell lines and two lines of normal (non-cancerous) mesothelial cells. They also studied cancer cells taken from fluid around the lungs (pleural effusions) of patients with mesothelioma or lung adenocarcinoma, and tumor samples removed at surgery from five patients with malignant pleural mesothelioma or poorly-differentiated lung adenocarcinoma. Nanotubes were most common in a low-serum, high-glucose, acidic growth medium. Through them, cells passed proteins, mitochondria and other cell contents, sometimes in both directions. Nanotubes formed between cancer cells and between normal cells. No nanotubes or exchange were seen between cancer cells and normal cells when the two were mixed. The drugs metformin, everolimus and latrunculin A each significantly reduced nanotube formation by 72 hours compared with controls. Nanotubes were seen in all five tumor samples. The authors noted that the tissue may have picked up dye non-specifically. They proposed that nanotubes play an important role in how cancer cells cause disease and invade.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) study of cultured cells, plus microscopic examination of tumor tissue removed from patients
• Who was studied: Mesothelioma cell lines MSTO-211H (biphasic), VAMT (sarcomatoid) and H-Meso (epithelioid). Two benign human mesothelial cell lines: LP9, from peritoneal mesothelium, and Met5A, from the pleural lining. Cancer cells from pleural effusions of patients with mesothelioma or lung adenocarcinoma. Fresh tumor specimens from five patients with malignant pleural mesothelioma or poorly-differentiated lung adenocarcinoma, obtained at Memorial Sloan-Kettering Cancer Center, New York.
• Exposure: No asbestos or fiber exposure was studied. The cells were exposed to different growth-medium conditions, including a low-serum (2.5% fetal calf serum), high-glucose (50 mM), acidic (pH 6.6) medium, and to the drugs metformin, everolimus and latrunculin A.
• Main results:
  • Nanotubes formed on their own in mesothelioma cell lines and in patient-derived cancer cells. They were most common in the acidic, high-glucose, low-serum medium.
  • Staining showed actin running along the whole length of the nanotubes in MSTO-211H mesothelioma cells.
  • In mesothelioma cells, nanotubes carried proteins, mitochondria, Golgi and other cell contents, both one way and in both directions.
  • When mesothelioma cells were mixed with normal mesothelial cells, no nanotubes or exchange were seen between the two kinds of cell. Nanotubes did form within each kind.
  • Mixed biphasic (MSTO) and sarcomatoid (VAMT) mesothelioma cell lines formed nanotubes with each other and exchanged contents.
  • In MSTO mesothelioma cells, metformin, everolimus and latrunculin A each significantly reduced nanotube formation by 72 hours compared with controls.
  • Metformin did not significantly affect how fast the cells multiplied.
  • Nanotubes were found in all five tumor specimens from patients with malignant pleural mesothelioma or lung adenocarcinoma.
• The authors' conclusion: The authors proposed that nanotubes provide a direct connection between the insides of invasive malignant mesothelioma cells, and that they play an important role in how cancer cells cause disease and invade.
• Limitations the authors state:
  • In the tumor tissue sections, the nanotubes or the tissue may have picked up fluorescent dye non-specifically.
  • The role of nanotubes forming between invasive cancer cells, seen in the scratch (wound) experiment, needs further evaluation.
  • How the transfer of mitochondria matters for cancer growth is not yet known.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Mesothelial Cells, Lung Adenocarcinoma.

Related studies

• The degree and kind of agglomeration affect carbon nanotube cytotoxicity — P. Wick, P. Manser, et al. (2007)
• Functionalized Scintillating Nanotubes for Simultaneous Radio- and Photodynamic Therapy of Cancer — I. Villa, C. Villa, et al. (2021)
• Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer — J. Liu, Y. Zhang, et al. (2021)
• Respiratory toxicity of multi-wall carbon nanotubes — J. Muller, F. Huaux, et al. (2005)
• Mineral-organic hybrid nanotubes as highly sensitive solid state optical chemical sensors — A. Monguzzi, I.G. Lesci, et al. (2014)
• Synthetic hydrosilicate nanotubes induce low pro-inflammatory and cytotoxic responses compared to natural chrysotile in lung cell cultures — T. Skuland, T. Maslennikova, et al. (2020)

Browse more research in PloS One, or return to medical research.