Lost in translation: applying 2D intercellular communication via tunneling nanotubes in cell culture to physiologically relevant 3D microenvironments

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Tunneling nanotubes (TNTs) are membranous conduits for direct cell-to-cell communication. Until the past decade, little had been known about their composite structure, function, and mechanisms of action in both normal physiologic conditions as well as in disease states. Now TNTs are attracting increasing interest for their key role(s) in the pathogenesis of disease, including neurodegenerative disorders, inflammatory and infectious diseases, and cancer. The field of TNT biology is still in its infancy, but inroads have been made in determining potential mechanisms and function of these remarkable structures. For example, TNTs function as critical conduits for cellular exchange of information; thus, in cancer, they may play an important role in critical pathophysiologic features of the disease, including cellular invasion, metastasis, and emergence of chemotherapy drug resistance. Although the TNT field is still in a nascent stage, we propose that TNTs can be investigated as novel targets for drug-based treatment of cancer and other diseases.

Original languageEnglish (US)
Pages (from-to)699-707
Number of pages9
JournalFEBS Journal
Issue number5
StatePublished - Mar 1 2017

Bibliographical note

Funding Information:
We thank Michael Franklin for excellent editorial suggestions and critical review of the manuscript. We especially wish to thank and acknowledge the contributions of Katia Manova-Todorova, Sho Fujisawa, and Yevgeniy Romin for their expert advice and assistance with microscopy imaging of TNTs over the years. Research reported and discussed in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 (KL2 award to EL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. In addition, this research has also been supported by Minnesota Masonic Charities; the Minnesota Medical Foundation/University of Minnesota Foundation; the Masonic Cancer Center and Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota; Institutional Research Grant #118198-IRG-58-001-52-IRG94 from the American Cancer Society; the National Pancreas Foundation; the Mezin-Koats Colon Cancer Research Award; The Randy Shaver Cancer Research and Community Fund; the Litman Family Fund for Cancer Research; the Baker Street Foundation; and the University of Minnesota Deborah E. Powell Center for Women's Health Interdisciplinary Seed Grant support (Grant #PCWH-2013-002).

Publisher Copyright:
© 2016 Federation of European Biochemical Societies


  • 3D cell biology
  • 3D confocal imaging
  • in vivo imaging
  • intercellular communication
  • intercellular transfer
  • membrane tubes
  • tunneling nanotubes


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