Endothelial-tumor cell interaction in brain and CNS malignancies

Maria Peleli, Aristidis Moustakas, Andreas Papapetropoulos

Research output: Contribution to journalReview articlepeer-review

Abstract

Glioblastoma and other brain or CNS malignancies (like neuroblastoma and medulloblastoma) are difficult to treat and are characterized by excessive vascularization that favors further tumor growth. Since the mean overall survival of these types of diseases is low, the finding of new therapeutic approaches is imperative. In this review, we discuss the importance of the interaction between the endothelium and the tumor cells in brain and CNS malignancies. The different mechanisms of formation of new vessels that supply the tumor with nutrients are discussed. We also describe how the tumor cells (TC) alter the endothelial cell (EC) physiology in a way that favors tumorigenesis. In particular, mechanisms of EC–TC interaction are described such as (a) communication using secreted growth factors (i.e., VEGF, TGF-β), (b) intercellular communication through gap junctions (i.e., Cx43), and (c) indirect interaction via intermediate cell types (pericytes, astrocytes, neurons, and immune cells). At the signaling level, we outline the role of important mediators, like the gasotransmitter nitric oxide and different types of reactive oxygen species and the systems producing them. Finally, we briefly discuss the current antiangiogenic therapies used against brain and CNS tumors and the potential of new pharmacological interventions that target the EC–TC interaction.

Original languageEnglish (US)
Article number7371
Pages (from-to)1-28
Number of pages28
JournalInternational journal of molecular sciences
Volume21
Issue number19
DOIs
StatePublished - Oct 1 2020

Keywords

  • Angiogenesis
  • Brain tumors
  • Endothelium
  • Gap junctions
  • Glioblastoma
  • Nitric oxide
  • Reactive oxygen species
  • TGF-β
  • VEGF

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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