Tunneling Nanotubes: A new paradigm for studying intercellular communication and therapeutics in cancer

Our plain-English summary of Tunneling Nanotubes: A new paradigm for studying intercellular communication and therapeutics in cancer, by E. Lou, S. Fujisawa, A. Barlas, et al (Communicative & Integrative Biology, 2012).

The study

• Authors: E. Lou, S. Fujisawa, A. Barlas, Y. Romin, K. Manova-Todorova, M.A. Moore, S. Subramanian
• Journal: Communicative & Integrative Biology
• Published: 2012;5(4):399-403
• Cited by: 91 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Tunneling nanotubes are actin-based cytoplasmic extensions that function as intercellular channels in a wide variety of cell types.There is a renewed and keen interest in the examination of modes of intercellular communication in cells of all types, especially in the field of cancer biology. Tunneling nanotubes -which in the literature have also been referred to as "membrane nanotubes," "'intercellular' or 'epithelial' bridges," or "cytoplasmic extensions" - are under active investigation for their role in facilitating direct intercellular communication. These structures have not, until recently, been scrutinized as a unique and previously unrecognized form of direct cell-to-cell transmission of cellular cargo in the context of human cancer. Our recent study of tunneling nanotubes in human malignant pleural mesothelioma and lung adenocarcinomas demonstrated efficient transfer of cellular contents, including proteins, Golgi vesicles, and mitochondria, between cells derived from several well-established cancer cell lines. Further, we provided effective demonstration that such nanotubes can form between primary malignant cells from human patients. For the first time, we also demonstrated the in vivo relevance of these structures in humans, having effectively imaged nanotubes in intact solid tumors from patients. Here we provide further analysis and discussion on our findings, and offer a prospective 'road map' for studying tunneling nanotubes in the context of human cancer. We hope that further understanding of the mechanisms, methods of transfer, and particularly the role of nanotubes in tumor-stromal cross-talk will lead to identification of new selective targets for cancer therapeutics.

In plain English

This article was a short addendum (a commentary) in which the authors discussed their own earlier study, published in PLoS One in 2012, and set out a plan for future research. It did not study asbestos or asbestos exposure. Tunneling nanotubes are long, thin, actin-based extensions that connect cells. The authors summarized their earlier findings in malignant mesothelioma cells. In that work, proteins, Golgi vesicles and mitochondria passed between cells through these nanotubes. Nanotubes were found in cells from patient specimens and from established cancer cell lines, and they were described as existing in solid tumors in patients. The authors also stated that the medications metformin and everolimus suppressed nanotube formation in that work. Images in this article showed nanotubes connecting MSTO-211H mesothelioma cells. The authors proposed questions for future study, including the role of nanotubes in invasion and metastasis, and proposed standard names for these structures. They noted that this research is at an early stage. They hoped it may lead to new, selective targets for cancer therapy.

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: Article addendum (commentary) discussing the authors' own earlier PLoS One study and proposing a research 'road map'; not a new study with measured results
• Who was studied: In the earlier study discussed: malignant mesothelioma and lung cancer cells from established cancer cell lines and from human patient specimens; images in this article show the MSTO-211H mesothelioma cell line
• Exposure: No asbestos or other fiber exposure was studied. The subject was tunneling nanotubes, which are connections between cells.
• Main results:
  • The authors restated that their earlier study showed transfer of proteins, Golgi vesicles and mitochondria between malignant mesothelioma cells through tunneling nanotubes
  • The authors stated that their earlier work showed tunneling nanotubes exist in solid tumors in patients, not only in laboratory cultures
  • The authors stated that, in their earlier work, metformin and everolimus suppressed tunneling nanotube formation
  • Figures in this article showed tunneling nanotubes connecting MSTO-211H mesothelioma cells
  • The authors proposed future research questions, including the role of nanotubes in invasion and metastasis
  • The authors proposed standard naming ('Tunneling Nanotubes', TNT or TnT) for these structures in future publications
• The authors' conclusion: The authors concluded that identifying unique aspects of tunneling nanotubes between cancer cells may lead to new specific and selective targets for cancer therapy
• Limitations the authors state:
  • The authors stated that the study of tunneling nanotubes is still at its earliest stages
  • The authors stated that structures reported under different names may be structurally or functionally different
  • The authors stated that it remains to be determined whether any components of these nanotubes are truly cancer-specific

Topics

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

Related studies

• Intercellular communication in malignant pleural mesothelioma: properties of tunneling nanotubes — J.W. Ady, S. Desir, et al. (2014)
• Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma — E. Lou, S. Fujisawa, et al. (2012)
• Treatment with tumor-treating fields (TTFields) suppresses intercellular tunneling nanotube formation in vitro and upregulates immuno-oncologic biomarkers in vivo in malignant mesothelioma — A. Sarkari, S. Korenfeld, et al. (2023)
• Expression of cell adhesion molecules and connexins in gap junctional intercellular communication deficient human mesothelioma tumour cell lines and communication competent primary mesothelial cells — K. Pelin, A. Hirvonen, et al. (1994)
• Metsovo-tremolite asbestos fibres: in vitro effects on mutation, chromosome aberration, cell transformation and intercellular communication — K. Athanasiou, S.H. Constantopoulos, et al. (1992)
• Tunneling nanotubes: an alternate route for propagation of the bystander effect following oncolytic viral infection — J. Ady, V. Thayanithy, et al. (2016)

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