The extracellular matrix niche microenvironment of neural and cancer stem cells in the brain

Abstract

Numerous studies demonstrated that neural stem cells and cancer stem cells (NSCs/CSCs) share several overlapping characteristics such as self-renewal, multipotency and a comparable molecular repertoire. In addition to the intrinsic cellular properties, NSCs/CSCs favor a similar environment to acquire and maintain their characteristics. In the present review, we highlight the shared properties of NSCs and CSCs in regard to their extracellular microenvironment called the NSC/CSC niche. Moreover, we point out that extracellular matrix (ECM) molecules and their complementary receptors influence the behavior of NSCs/CSCs as well as brain tumor progression. Here, we focus on the expression profile and functional importance of the ECM glycoprotein tenascin-C, the chondroitin sulfate proteoglycan DSD-1-PG/phosphacan but also on other important glycoprotein/proteoglycan constituents. Within this review, we specifically concentrate on glioblastoma multiforme (GBM). GBM is the most common malignant brain tumor in adults and is associated with poor prognosis despite intense and aggressive surgical and therapeutic treatment. Recent studies indicate that GBM onset is driven by a subpopulation of CSCs that display self-renewal and recapitulate tumor heterogeneity. Based on the CSC hypothesis the cancer arises just from a small subpopulation of self-sustaining cancer cells with the exclusive ability to self-renew and maintain the tumor. Besides the fundamental stem cell properties of self-renewal and multipotency, GBM stem cells share further molecular characteristics with NSCs, which we would like to review in this article.

Keywords: Brain tumor; Cancer stem cells; Chondroitinsulfate proteoglycans; Extracellular matrix; Glioblastoma multiforme; Neural stem cells; Phosphacan; Stem cell niche; Tenascin-C.