Breast Cancer Cells Extravasation Across the Blood-Brain Barrier: From Basic to Translational Research

Brain metastases (BM) are among the most impacting factors associated with decreased life expectancy of breast cancer (BC) patients, namely due to the restricted permeability of the blood-brain barrier (BBB) that precludes the entrance of most drugs into the brain. Although extravasation is a crucial process for BM establishment, the events occurring at the brain microvasculature, and particularly at the BBB level, are mostly undetermined. Therefore, there is an unmet need to understand the events that precede BM formation, to develop preventive therapeutics, and to safeguard BC patients from the harmful consequences of the metastatic progress. In this review, we bring together recent advances in the cellular and molecular mechanisms underlying the extravasation and the current tools and models for its study. Recent studies revealed that BC cells (BCCs) extravasation across the BBB involves complex direct and non-direct interactions. Such interactions result in the activation of several signalling pathways that culminate in cellular phenotypic and morphological alterations that pinpoint therapeutic targets. Importantly, better cellular and animal models for the study of extravasation have been implemented, which translate into greater confidence in the results and consequently in enhanced success in clinical trials. Improved understanding of BCCs extravasation through the BBB, as well as the availability of superior tools and models to its study are essential steps to discover new BM preventive therapeutic options and to improve BC patients’ life expectancy and quality.