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Extracellular Vesicles in Brain Tumor Progression.

Esterina D'Asti1, Shilpa Chennakrishnaiah1, Tae Hoon Lee1

  • 1RI MUHC, Montreal Children's Hospital, McGill University, 1001 Decarie Blvd, E M1 2244, Montreal, QC, H4A 3J1, Canada.

Cellular and Molecular Neurobiology
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PubMed
Summary

Brain tumors are complex ecosystems where extracellular vesicles (EVs) mediate intercellular communication and horizontal molecular transfer. These EVs, carrying oncogenic drivers, play crucial roles in brain tumor progression and offer potential as biomarkers.

Keywords:
CancerExosomesExtracellular vesiclesGlioblastomaMedulloblastomaOncogenes

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Area of Science:

  • Neuro-oncology
  • Cell Biology
  • Molecular Oncology

Background:

  • Brain tumors exhibit complex multicellular ecosystems with intrinsic genetic and epigenetic alterations.
  • Cell-intrinsic changes in brain tumors can be viewed as adaptations to microenvironmental factors.
  • Oncogenic events influence the tumor microenvironment via the cellular secretome, including extracellular vesicles (EVs).

Purpose of the Study:

  • To explore the role of extracellular vesicles (EVs) in brain tumor ecosystems.
  • To understand how EVs mediate intercellular communication and molecular transfer in brain tumors.
  • To investigate the potential of EVs as biomarkers for brain tumor diagnosis and therapy.

Main Methods:

  • Analysis of EV heterogeneity and nomenclature (exosomes, microvesicles, microparticles).
  • Investigation of EV cargo, including lipids, proteins, mRNA, non-coding RNA, and DNA.
  • Examination of EV roles in intercellular communication, horizontal molecular transfer, and biological activity in the central nervous system and cancer.
  • Analysis of EV profiles (vesiculome) in different glioblastoma subtypes.

Main Results:

  • EVs are heterogeneous carriers of molecular cargo, facilitating intercellular communication and horizontal molecular transfer.
  • In brain tumors, EVs regulate cell growth, angiogenesis, and tumor-stromal interactions.
  • EVs from brain tumors can carry oncogenic drivers (e.g., EGFRvIII in glioblastoma), termed 'oncosomes', transferring mutant oncoproteins and nucleic acids.
  • Oncogenic pathways modulate EV biogenesis, cargo, and release, with distinct EV-regulating gene profiles observed in glioblastoma subtypes.

Conclusions:

  • Extracellular vesicles are integral components of brain tumor ecosystems, mediating communication and influencing tumor progression.
  • EVs, particularly 'oncosomes', can transfer oncogenic drivers between cells, altering tumor phenotypes.
  • The molecular cargo and profiles of EVs suggest context-specific roles in brain tumor progression.
  • Circulating EVs in biofluids hold promise as biomarker reservoirs for guiding diagnostic and therapeutic decisions in neuro-oncology.