Role of the blood-brain barrier in the formation of brain metastases

Imola Wilhelm, Judit Molnár, Csilla Fazakas, János Haskó, István A. Krizbai

Research output: Contribution to journalReview article

74 Citations (Scopus)

Abstract

The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB). The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting metastatic cells during extravasation and proliferation in the brain. The mechanisms of interaction of cancer cells and cerebral endothelial cells are largely uncharacterized. Here, we provide a comprehensive review on our current knowledge about the role of junctional and adhesion molecules, soluble factors, proteolytic enzymes and signaling pathways mediating the attachment of tumor cells to brain endothelial cells and the transendothelial migration of metastatic cells. Since brain metastases represent a great therapeutic challenge, it is indispensable to understand the mechanisms of the interaction of tumor cells with the BBB in order to find targets of prevention of brain metastasis formation.

Original languageEnglish
Pages (from-to)1383-1411
Number of pages29
JournalInternational journal of molecular sciences
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Astrocyte
  • Blood-brain barrier
  • Breast cancer
  • Central nervous system
  • Cerebral endothelial cell
  • Lung cancer
  • Melanoma
  • Metastasis
  • Paracellular transmigration
  • Tight junction

ASJC Scopus subject areas

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

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