Blood-brain Barrier Remodeling during Brain Metastasis Formation

Abstract

Our understanding of the process of metastatic progression has improved markedly over the past decades, yet metastasis remains the most enigmatic component of cancer pathogenesis. This lack of knowledge has serious health-related implications, since metastasis is responsible for 90% of all cancer-related mortalities. The brain is considered a sanctuary site for metastatic tumor growth, where the blood-brain barrier (BBB) and other components of the brain microenvironment, provide protection to the tumor cells from immune surveillance, chemotherapeutics and other potentially harmful substances. The interactions between tumor cells and the brain microenvironment, principally brain vascular endothelium, are the critical determinants in their progression toward metastasis, dormancy, or clearance. This review discusses current knowledge of the biology of metastatic progression, with a particular focus on the tumor cell migration and colonization in the brain. online address: http://www.molmed.org

Mystery of the brain metastatic disease in breast cancer patients: improved patient stratification, disease prediction and targeted prevention on the horizon?

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EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer

“…Brain is considered to be a sanctuary site because of the blood–brain barrier (BBB). The BBB is a physiological obstruction to the delivery of systemic therapies to the brain parenchyma and central nervous system (CNS) [15] and it plays a key role in tumor cell migration and colonization to the brain [16]. For these reasons, there are large differences in biomarkers expressed between the primary tumor and metastases, especially for BM [17].…”

Management of Brain Metastases from Solid Tumors

“…Endothelial cells of brain vessels serve as a mechanical barrier, and astrocytes and microglia are capable of destroying tumor cells. However, after brain colonization, the cerebral endothelial cells, astrocytes, and microglia provide crucial support in the growth and proliferation of tumor cells, and BBB protects cancer cells from influencing the immune system and most anticancer drugs [9].…”

“…The availability of MELTF on the melanoma cell membrane determines their ability to penetrate through the BBB. High levels of STAT3 in melanoma BM compared to primary tumor cells indicate a relationship between STAT3 expression and tumor cell migration to the brain [9]. Thus, the identification of tumor cells specific markers of penetration through the BBB can be a basis for the development of specific methods for the prevention of BM.…”