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Microvesicles as mediators of intercellular communication in cancer—the emerging science of cellular ‘debris’

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Abstract

Cancer cells emit a heterogeneous mixture of vesicular, organelle-like structures (microvesicles, MVs) into their surroundings including blood and body fluids. MVs are generated via diverse biological mechanisms triggered by pathways involved in oncogenic transformation, microenvironmental stimulation, cellular activation, stress, or death. Vesiculation events occur either at the plasma membrane (ectosomes, shed vesicles) or within endosomal structures (exosomes). MVs are increasingly recognized as mediators of intercellular communication due to their capacity to merge with and transfer a repertoire of bioactive molecular content (cargo) to recipient cells. Such processes may occur both locally and systemically, contributing to the formation of microenvironmental fields and niches. The bioactive cargo of MVs may include growth factors and their receptors, proteases, adhesion molecules, signalling molecules, as well as DNA, mRNA, and microRNA (miRs) sequences. Tumour cells emit large quantities of MVs containing procoagulant, growth regulatory and oncogenic cargo (oncosomes), which can be transferred throughout the cancer cell population and to non-transformed stromal cells, endothelial cells and possibly to the inflammatory infiltrates (oncogenic field effect). These events likely impact tumour invasion, angiogenesis, metastasis, drug resistance, and cancer stem cell hierarchy. Ongoing studies explore the molecular mechanisms and mediators of MV-based intercellular communication (cancer vesiculome) with the hope of using this information as a possible source of therapeutic targets and disease biomarkers in cancer.

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Fig. 1

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Abbreviations

MVs:

Microvesicles

TF:

Tissue factor

EGFR:

Epidermal growth factor receptor

EGFRvIII:

Mutant EGFR (variant III)

GBM:

Glioblastoma multiforme

IL-6:

Interleukin-6

IL-8:

Interleukin-8

mRNA:

Messenger ribonucleic acid

PS:

Phosphatidylserine

RTK:

Receptor tyrosine kinase

VEGF:

Vascular endothelial growth factor

VEGFR-2:

VEGF receptor 2

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Acknowledgements

This work was supported by grants from the Canadian Cancer Society Research Institute (CCSRI) and Canadian Institutes of Health Research (CIHR) to J.R. who is a holder of the Jack Cole Chair in Pediatric Oncology at McGill University.

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Authors and Affiliations

  1. Montreal Children’s Hospital Research Institute, McGill University, 4060 Ste Catherine West, Montreal, QC, H3Z 2Z3, Canada

    Tae Hoon Lee, Esterina D’Asti, Nathalie Magnus, Khalid Al-Nedawi, Brian Meehan & Janusz Rak

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  1. Tae Hoon Lee
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  2. Esterina D’Asti
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  3. Nathalie Magnus
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  4. Khalid Al-Nedawi
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Correspondence to Janusz Rak.

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Tae Hoon Lee and Esterina D'Asti equally contributed to this article.

This article is published as part of the Special Issue on Small Vesicles as Immune Modulators.

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Lee, T.H., D’Asti, E., Magnus, N. et al. Microvesicles as mediators of intercellular communication in cancer—the emerging science of cellular ‘debris’. Semin Immunopathol 33, 455–467 (2011). https://doi.org/10.1007/s00281-011-0250-3

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  • DOI: https://doi.org/10.1007/s00281-011-0250-3

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