Abstract
Cellular communication is important in all aspects of tissue and organism functioning, from the level of single cells, two discreet populations, and distant tissues of the body. Long distance communication networks integrate individual cells into tissues to maintain a complex organism during development, but when communication between cells goes awry, disease states such as cancer emerge. Herein we discuss the growing body of evidence suggesting that communication methods known to be employed by neurons, also exist in other cell types. We identify three major areas of long-distance communication: bioelectric signaling, tunneling nanotubes (TNTs), and macrophage modulation of networks, and draw comparisons about how these systems operate in the context of development and cancer. Bioelectric signaling occurs between cells through exchange of ions and tissue-level electric fields, leading to changes in biochemical gradients and molecular signaling pathways to control normal development and tumor growth and invasion in cancer. TNTs transport key morphogens and other cargo long distances, mediating electrical coupling, tissue patterning, and malignancy of cancer cells. Lastly macrophages maintain long distance signaling networks through trafficking of vesicles during development, providing communication relays and priming favorable microenvironments for cancer metastasis. By drawing comparisons between non-neural long distance signaling in the context of development and cancer we aim to encourage crosstalk between the two fields to cultivate new hypotheses and potential therapeutic strategies.
Highlights
Specialty section: This article was submitted to Signaling, a section of the journal Frontiers in Cell and Developmental
We identify three major areas of long-distance communication: bioelectric signaling, tunneling nanotubes (TNTs), and macrophage modulation of networks, and draw comparisons about how these systems operate in the context of development and cancer
Work in cultured neural crest cells as well as in glioma (Kirson et al, 2007) has shown that distant cells connected by TNTs can be electrically coupled (Wang et al, 2010; Wang and Gerdes, 2012) via gap junctions, providing a possible mechanism for these long-distance effects, though this model lacks in vivo testing
Summary
In this review we present an overview of recent findings uncovering a primitive non-neural network of connected cellular projections that enables cells to communicate at a distance. We discuss the potential of these networks to enable longdistance physiological signaling. We discuss evidence that macrophages control connectivity within this network. Throughout the review we draw on complementary examples from developmental biology and cancer literature, analyzing similarities between the two, and highlighting knowledge gaps in one field that may be filled with information from the other (Table 1). We hope to bring this emerging paradigm to the attention of a wide range of basic and applied researchers
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