Glioblastoma Stem Cells and Their Microenvironment

Glioblastoma (GBM) is the most common primary malignant astrocytoma associated with a poor patient survival. Apart from arising de novo, GBMs also occur due to progression of slower growing grade III astrocytomas. GBM is characterized by extensive hypoxia, angiogenesis, proliferation and invasion. Standard treatment options such as surgical resection, radiation therapy and chemotherapy have increased median patient survival to 14.6 months in adults but recurrent disease arising from treatment resistant cancer cells often results in patient mortality. These treatment resistant cancer cells have been found to exhibit stem cell like properties. Strategies to identify or target these Glioblastoma Stem Cells (GSC) have proven to be unsuccessful so far. Studies on cancer stem cells (CSC) within GBM and other cancers have highlighted the importance of paracrine signaling networks within their microenvironment on the growth and maintenance of CSCs. The study of GSCs and their communication with various cell populations within their microenvironment is therefore not only important to understand the biology of GBMs but also to predict response to therapies and to identify novel targets which could stymy support to treatment resistant cancer cells and prevent disease recurrence. The purpose of this chapter is to introduce the concept of GSCs and to detail the latest findings indicating the role of various cellular subtypes within their microenvironment on their survival, proliferation and differentiation.