Foe or friend? Janus-faces of the neurovascular unit in the formation of brain metastases

Wilhelm, Imola Mária and Fazakas, Csilla and Molnár, Kinga and Végh, Attila Gergely and Haskó, János and Krizbai, István Adorján (2017) Foe or friend? Janus-faces of the neurovascular unit in the formation of brain metastases. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM. ISSN 0271-678X

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Abstract

Despite the potential obstacle represented by the blood-brain barrier for extravasating malignant cells, metastases are more frequent than primary tumors in the central nervous system. Not only tightly interconnected endothelial cells can hinder metastasis formation, other cells of the brain microenvironment (like astrocytes and microglia) can also be very hostile, destroying the large majority of metastatic cells. However, malignant cells that are able to overcome these harmful mechanisms may benefit from the shielding and even support provided by cerebral endothelial cells, astrocytes and microglia, rendering the brain a sanctuary site against anti-tumor strategies. Thus, cells of the neurovascular unit have a Janus-faced attitude towards brain metastatic cells, being both destructive and protective. In this review, we present the main mechanisms of brain metastasis formation, including those involved in extravasation through the brain vasculature and survival in the cerebral environment.

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