The emerging roles of cerebral pericytes in brain metastasis

Brain metastases are a prevalent disease found in up to 40% of patients with solid cancers, and are associated with significant morbidity and mortality. Current treatment options for brain metastases are limited, especially because the tumor is protected by the blood-tumor barrier that prevents the penetration of chemotherapeutic agents. Understanding the brain metastatic process and the cells involved is required to discover new treatment approaches. One interesting therapeutic target is mural cells called pericytes, given their importance in maintaining the blood-brain barrier, regulating blood flow, modulating the immune response, and promoting angiogenesis in normal brain physiology. The role of cerebral pericytes in the initiation and maintenance of brain metastases is not well understood. In this review, we discuss the current understanding of the steps in the metastatic process and the roles of cerebral pericytes at each step, especially premetastatic niche formation, cancer cell extravasation, brain micrometastasis formation, and maintenance of macrometastasis and the tumor microenvironment. This study aims to provide a comprehensive understanding of the importance of brain pericytes in brain metastasis formation and maintenance, offer a perspective on the further investigations that are needed, and propose possible clinical implications for the treatment of brain metastases.