Abstract
Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.
Highlights
Malignant gliomas represent some of the greatest challenges in the management of cancer patients worldwide
Primary brain tumors are considered amongst the most refractory malignancies and their most aggressive form, glioblastoma multiform (GBM, WHO grade IV), is the most common and lethal subtype [1]
neural stem cell (NSC) are located in specific regions of the brain called neurogenic niches which retain the ability to produce neurons and glia throughout life, functioning as a source of stem cells and progenitors in adults [17,18]
Summary
Malignant gliomas represent some of the greatest challenges in the management of cancer patients worldwide. NSCs are located in specific regions of the brain called neurogenic niches which retain the ability to produce neurons and glia throughout life, functioning as a source of stem cells and progenitors in adults [17,18] Those niches are essential to control critical stem cell properties, to feed the NSCs and to support their self-renewal abilities. Periventricular adult NSCs express high levels of glial fibrillary acidic protein (GFAP) which raised exciting questions on whether or not astrocytes could be involved in GBM initiation Following those observations, two major hypotheses have been put forward: the astrocytes dedifferentiation theory and the glioblastoma stem cell theory
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