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• Wilhelm, I
• Molnár, J
• Fazakas, C
• Haskó, J
• Krizbai, IA.
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• Wilhelm, I
• Molnár, J
• Fazakas, C
• Haskó, J
• Krizbai, IA.
• [+] on PubMed
• Wilhelm, I
• Molnár, J
• Fazakas, C
• Haskó, J
• Krizbai, IA.

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Int. J. Mol. Sci. 2013, 14(1), 1383-1411; doi:10.3390/ijms14011383

Review

Role of the Blood-Brain Barrier in the Formation of Brain Metastases

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

Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary

* Author to whom correspondence should be addressed.

Received: 17 October 2012; in revised form: 12 December 2012 / Accepted: 14 December 2012 / Published: 11 January 2013

(This article belongs to the Special Issue Brain Metastasis)

Download PDF Full-Text [597 KB, uploaded 11 January 2013 11:38 CET]

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.

Keywords: blood-brain barrier; cerebral endothelial cell; tight junction; paracellular transmigration; astrocyte; central nervous system; metastasis; breast cancer; lung cancer; melanoma

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