Intercellular communication is a vital yet underdeveloped aspect of cancer pathobiology. This Opinion article reviews the importance and challenges of microscopic imaging of tunneling nanotubes (TNTs) in the complex tumor microenvironment. The use of advanced microscopy to characterize TNTs in vitro and ex vivo, and related extensions called tumor microtubes (TMs) reported in gliomas in vivo, has propelled this field forward. This topic is important because the identification of TNTs and TMs fills the gap in our knowledge of how cancer cells communicate at long range in vivo, inducing intratumor heterogeneity and resistance to treatment. Here we discuss the concept that TNTs/TMs fill an important niche in the ever-changing microenvironment and the role of advanced microscopic imaging to elucidate that niche. Direct cell-to-cell communication between cellular conduits called tunneling nanotubes (TNTs) and tumor microtubes (TMs) is an emerging and novel concept in cancer cell biology. Over the past decade, the field has moved from studies in vitro to the examination of tumors ex vivo and, more recently, in vivo studies in animal models. Advanced microscopy techniques, including but not limited to confocal imaging, electron microscopy, stimulated emission depletion microscopy, and in vivo laser scanning microscopy, are being harnessed to better characterize the structure of TNTs and TMs at high resolution. More studies are needed to identify the function and mechanisms of TNTs and to determine the extent to which there is heterogeneity between different cell types.
Bibliographical noteFunding Information:
The authors thank Michael Franklin for excellent editorial suggestions and critical review of the manuscript. They also thank Guillermo Marques and Mark Sanders for helpful assistance with confocal microscopy performed at the University Imaging Centers at the University of Minnesota. The authors regret that, due to space limitations, many excellent publications in this field could not be cited. They thank all researchers who have dedicated their efforts to advancing research on this topic. This research was supported by: an NIH Clinical and Translational Science KL2 Scholar Award ( 8UL1TR000114 to E.L.); 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 ). The Molecular Cytology Core Facility at Memorial Sloan-Kettering Cancer Center (MSKCC) is supported by MSKCC Cancer Center Support Grant 2 P30 CA008748-48 .
© 2017 Elsevier Inc.
- cancer cell biology
- in vivo imaging
- intercellular communication
- tumor microtubes
- tunneling nanotubes