The involvement of cancer stem cells in brain metastatic process

Abstract

Metastatic brain tumor is the most common intracranial malignant brain tumor. Although the development of molecular target drugs improved the regulation of clinical features of primary tumor in patients, the incidence of brain metastases is increasing. Because brain metastasis by the primary tumor become a major limitation of quality of life for many cancer patients, understanding the mechanism of brain metastasis is required for development of effective therapies. On the other hand, accumulating evidence indicated that individual tumors display the cellular heterogeneity generated by the cancer stem cells. This cancer stem cell model leads us to consider how cancer stem cells are associated with tumor metastasis. Here we review the metastatic process so-called multistep metastatic cascade including detachment from the primary tumor, invasion, intravasation, transit to distant organ, extravasation and proliferation at secondary site, and the involvement of cancer stem cells in each process. In addition, we also introduce the recently emerging evidence for brain metastasis initiating cells with our current research.