The origin of brain malignancies at the blood–brain barrier

Research output: Contribution to journalReview articleContributedpeer-review



Despite improvements in extracranial therapy, survival rate for patients suffering from brain metastases remains very poor. This is coupled with the incidence of brain metastases continuing to rise. In this review, we focus on core contributions of the blood–brain barrier to the origin of brain metastases. We first provide an overview of the structure and function of the blood–brain barrier under physiological conditions. Next, we discuss the emerging idea of a pre-metastatic niche, namely that secreted factors and extracellular vesicles from a primary tumor site are able to travel through the circulation and prime the neurovasculature for metastatic invasion. We then consider the neurotropic mechanisms that circulating tumor cells possess or develop that facilitate disruption of the blood–brain barrier and survival in the brain’s parenchyma. Finally, we compare and contrast brain metastases at the blood–brain barrier to the primary brain tumor, glioma, examining the process of vessel co-option that favors the survival and outgrowth of brain malignancies.


Original languageEnglish
Article number282
JournalCellular and Molecular Life Sciences
Issue number10
Publication statusPublished - Oct 2023

External IDs

PubMed 37688612


Sustainable Development Goals


  • Brain metastasis, Cancer, Circulating tumor cells, Extracellular matrix, Metastatic niche, Neurovascular unit, Organotropism, Pre-metastatic niche, Tumor microenvironment, Humans, Extracellular Vesicles, Brain Neoplasms, Glioma, Biological Transport, Blood-Brain Barrier