Glioblastoma Stem Cells and Their Microenvironment

Abstract

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.

The Botanical Drug PBI-05204, a Supercritical CO2 Extract of Nerium Oleander, Inhibits Growth of Human Glioblastoma, Reduces Akt/mTOR Activities, and Modulates GSC Cell-Renewal Properties

“…GSCs have been found to contribute to the recurrence and resistance to therapies in malignant gliomas (Kamiya-Matsuoka and Gilbert, 2015). Emerging evidence suggested that GSCs are able to self-renew and are refractory to cancer treatment (Sattiraju et al, 2017). Lee DH et al reported that the cardiac glycoside, digitoxin, was capable of inhibiting the neurosphere formation and decreased CD133 expression in human GCSs cells (Lee et al, 2017).…”

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

“…216,217 These cells interact with the surrounding microenvironment, regulating multiple signaling networks such as VEGF, NF-kB, EGFR, HIF1α, TGFβ, BMP, and NOTCH for promotion of tumor growth, metastasis and angiogenesis. 218 In contrast, GASC are nontumorigenic tumor supporting stem cells originated from mesenchymal stem cells mostly found in the perivascular area. GASCs are classified into two categories according to their marker profile and functions.…”

Macrophage‐derived GPNMB accelerates skin healing

“…Stem cells have the capacity to self‐renew or differentiate into distinct cell populations . Mesenchymal stem cells have been identified in a variety of tissues, including the skin, where, by the formation of new cells, they guarantee the tissue repair after injuries.…”