Role of cell‐to‐cell communication in cancer: New features, insights, and directions

The current special issue entitled “Role of tunneling nanotubes (TNTs) in carcinogenesis” was designed to discuss the role of cell‐to‐cell communication, especially TNTs, in cancer pathogenesis. In addition, we discuss the exploitation of TNTs as a potential therapeutic target to prevent and reduce cancer incidence. It is accepted that cell‐to‐cell communication is essential for the development of multicellular systems, and it is coordinated by soluble factors, associated membrane proteins, exosomes, gap junction channels, and TNTs. An old belief in the cancer field is that cancer cells are “disconnected” from healthy cells, resulting in loss of cell‐to‐cell communication and neighbor control. However, recent data obtained from different kind of tumors indicate that TNTs and others forms of communication (exosomes and localized cell‐to‐cell communication) are highly expressed and functional during tumor development . In physiological conditions, TNTs are expressed by few cells, and their main function is to coordinate long‐distance signaling. However, upon carcinogenesis, TNTs proliferate and provide an alternative route of communication to enable the transfer of several signaling molecules and organelles to spread disease and toxicity. We propose that TNTs and their cargo are an attractive therapeutic target to reduce or prevent cancer development. All these unique aspects of cell‐to‐cell diffusion and organelle sharing will be discussed in this special issue.

[1]  L. Pleyer,et al.  Reactivation of dormant anti-tumor immunity – a clinical perspective of therapeutic immune checkpoint modulation , 2017, Cell Communication and Signaling.

[2]  W. Wick,et al.  Harmful networks in the brain and beyond , 2018, Science.

[3]  Douglas Hanahan,et al.  Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment Prospects and Obstacles for Therapeutic Targeting of Function-enabling Stromal Cell Types , 2022 .

[4]  T. Kornberg,et al.  Paracrine signaling mediated at cell–cell contacts , 2015, BioEssays : news and reviews in molecular, cellular and developmental biology.

[5]  P. Rojas-Ríos,et al.  Cytoneme-Mediated Delivery of Hedgehog Regulates the Expression of Bone Morphogenetic Proteins to Maintain Germline Stem Cells in Drosophila , 2012, PLoS biology.

[6]  H. Gerdes,et al.  Tunneling nanotubes , 2014, Communicative & integrative biology.

[7]  L. Cope,et al.  Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  From inflammation to gastric cancer – the importance of Hedgehog/GLI signaling in Helicobacter pylori-induced chronic inflammatory and neoplastic diseases , 2017, Cell Communication and Signaling.

[9]  Targeting MIR155HG in glioma: a novel approach. , 2017, Neuro-oncology.

[10]  K. Bhat,et al.  The Impact of the Tumor Microenvironment on the Properties of Glioma Stem-Like Cells , 2017, Front. Oncol..

[11]  O. Garaschuk,et al.  Brain tumour cells interconnect to a functional and resistant network , 2015, Nature.

[12]  N. Gorfinkiel,et al.  Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium , 2011, Proceedings of the National Academy of Sciences.

[13]  I. Guerrero,et al.  Balancing Hedgehog, a retention and release equilibrium given by Dally, Ihog, Boi and shifted/DmWif. , 2013, Developmental biology.

[14]  E. Kremmer,et al.  LST1 promotes the assembly of a molecular machinery responsible for tunneling nanotube formation , 2013, Journal of Cell Science.

[15]  Isabel Guerrero,et al.  Cytonemes are required for the establishment of a normal Hedgehog morphogen gradient in Drosophila epithelia , 2013, Nature Cell Biology.

[16]  Pieter Wesseling,et al.  The immunosuppressive tumour network: myeloid‐derived suppressor cells, regulatory T cells and natural killer T cells , 2013, Immunology.

[17]  Makoto Sato,et al.  FGF is an essential mitogen and chemoattractant for the air sacs of the drosophila tracheal system. , 2002, Developmental cell.

[18]  Maria Barna,et al.  Specialized filopodia direct long-range transport of Shh during vertebrate tissue patterning , 2013, Nature.

[19]  D. McClay,et al.  Dynamics of thin filopodia during sea urchin gastrulation. , 1995, Development.

[20]  T. Kornberg,et al.  Cytoneme-Mediated Contact-Dependent Transport of the Drosophila Decapentaplegic Signaling Protein , 2014, Science.

[21]  C. Zurzolo,et al.  Wiring through tunneling nanotubes – from electrical signals to organelle transfer , 2012, Journal of Cell Science.

[22]  W. Wick,et al.  Anti-Angiogenics: Their Role in the Treatment of Glioblastoma , 2018, Oncology Research and Treatment.

[23]  L. Postovit,et al.  Nodal signalling in embryogenesis and tumourigenesis. , 2013, The international journal of biochemistry & cell biology.

[24]  Paul G. McMenamin,et al.  Cutting Edge: Membrane Nanotubes In Vivo: A Feature of MHC Class II+ Cells in the Mouse Cornea1 , 2008, The Journal of Immunology.

[25]  H. Gerdes,et al.  Tunneling nanotubes, an emerging intercellular communication route in development , 2013, Mechanisms of Development.

[26]  Anna-Katerina Hadjantonakis,et al.  Dynamic imaging of mammalian neural tube closure. , 2010, Developmental biology.

[27]  S. Wessler,et al.  The sound of tumor cell-microenvironment communication – composed by the Cancer Cluster Salzburg research network , 2017, Cell Communication and Signaling.

[28]  In vivo evidence for short- and long-range cell communication in cranial neural crest cells , 2004, Development.

[29]  T. Kornberg The contrasting roles of primary cilia and cytonemes in Hh signaling. , 2014, Developmental biology.

[30]  S. Heiland,et al.  Tweety-Homolog 1 Drives Brain Colonization of Gliomas , 2017, The Journal of Neuroscience.

[31]  Sougata Roy,et al.  Specificity of Drosophila Cytonemes for Distinct Signaling Pathways , 2011, Science.

[32]  Sougata Roy,et al.  Cytonemes as specialized signaling filopodia , 2014, Development.

[33]  O. Shirihai,et al.  Miro1: New wheels for transferring mitochondria , 2014, The EMBO journal.

[34]  R. Barrio,et al.  Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion , 2014, Nature Communications.

[35]  S. Fraser,et al.  Intercellular Bridges in Vertebrate Gastrulation , 2011, PloS one.