Abstract
Intercellular communication among cancer cells and their microenvironment is crucial to disease progression. The mechanisms by which communication occurs between distant cells in a tumor matrix remain poorly understood. In the last two decades, experimental evidence from different groups proved the existence of thin membranous tubes that interconnect cells, named tunneling nanotubes, tumor microtubes, cytonemes or membrane bridges. These highly dynamic membrane protrusions are conduits for direct cell-to-cell communication, particularly for intercellular signaling and transport of cellular cargo over long distances. Tunneling nanotubes and tumor microtubes may play an important role in the pathogenesis of cancer. They may contribute to the resistance of tumor cells against treatments such as surgery, radio- and chemotherapy. In this review, we present the current knowledge about the structure and function of tunneling nanotubes and tumor microtubes in cancer and discuss the therapeutic potential of membrane tubes in cancer treatment.
Highlights
Intercellular communication can be occur through different indirect mechanisms such as secretion of cytokines and chemokines, microvesicles or exosomes
Recent findings revealed that glioma cells are capable of forming Tunneling nanotubes (TNT)/tumor microtubes (TMs) in vivo in correlation with the tumor’s metastatic potential and demonstrated that neurons can form synaptic contacts with TNTs/TMs from tumor cells
Pharmacological perturbation of TNTs/TMs consequentially reduced the metastatic potential of tumors in vivo in experimental metastasis models
Summary
Intercellular communication can be occur through different indirect mechanisms such as secretion of cytokines and chemokines, microvesicles or exosomes. Mounting evidence suggests that intercellular communication by TNTs and TMs may contribute to tumor survival and progression These membrane tubes can interlink cells over considerable distances. Cancer cells may be spread, so that direct communication via gap junctions, microvesicles or exosomes is improbable if not impossible In such cases, TNTs and TMs may act as spatial communication guides, allowing direct physical contact at distance between signal-sending and signal-receiving cell membranes. TNTs and TMs may act as spatial communication guides, allowing direct physical contact at distance between signal-sending and signal-receiving cell membranes They overcome the challenge of signal transport through tortuous structures within the tumor microenvironment and can provide spatial restriction, as well as specificity. TNTs and TMs support maintenance of tumor microenvironment and have been suggested to play an important role in tumor microenvironments
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