Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is the link?

Abstract

The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of BTSC and discuss the similarities between the characteristics of these cells and those of the endogenous population of neural stem cells (NPCs) residing in germinal areas of the adult brain. Finally, we propose possible mechanisms of cancer initiation and progression and suggest a model of tumor initiation that includes intrinsic changes of resident NSC and potential changes in the microenvironment defining the niche where the NSC reside.

Figure 1. Schematic relationship of the most frequent genetic deletions, mutations and amplifications detected in glioblastomas

The relative frequency is listed in parenthesis.

Figure 2. Potential mechanisms of oncogenic transformation of neural stem cells

A: physiological conditions are characterized by a controlled response of the neural stem cell to signals derived from the niche and responsible for affecting proliferation, survival and differentiation. B: alterations of the niche may contribute to modifying the properties of the cells. C: intrinsic alterations of genes and microRNAs within the cells modify their properties and render them prone to mechanisms of amplification and de-differentiation.

Figure 3

Schematic representation of the cell cycle regulatory networks as discussed in the text.