Stem Cell Microenvironments and Beyond

125

transform upon genetic mutations and microenvironmental cues to give rise to CSCs
(Hanahan and Weinberg 2011 ; Friedmann-Morvinski and Verma 2014 ). These CSCs
could later give rise to progenitor cancer cells and terminally differentiated cancer
cells. The other line of thought assumes that normal stem cells already present in
various organs undergo genetic mutations and react to aberrant paracrine signaling
within their microenvironment to give rise to altered undifferentiated malignant
stem cells. These deviant stem cells can then give rise to aberrant progenitor cells
with unregulated proliferative capabilities and later terminally differentiated cancer
cells (Kreso and Dick John 2014 ; Reya et al. 2001 ; Tan et al. 2006 ) (Fig. 7.1).

7.2.3 Role of the Microenvironment in Maintenance

of Glioblastomas Stem Cells

The site of origin of GSCs, either from a defined COIs or through de-differentiation
from somatic GBM cells, is highly dependent on the microenvironment and the
paracrine signaling networks. It is therefore important to understand the interactions
of actors in the vicinity of established tumors.

Heterogeneous

tumor

NSC CSC

CPC

CSCmuta

CPCmuta

C-TDC C-TDCmutb

C-TDCmuta

Clone# 1 mut a

Clone# 2 mut a+b

Clone#3mut a+c

Clone# 4 mut a+d

Clone #5mut a+b+e

Clone# 6 mut a+c+f

Stochastic model

Hierarchical

model

Self-renewal

Asymmetric

division

De

• differentiatio

n

De

• d
  iddfifff
  effrerr
  nt
  iat
  ion

mut

mut

Heterogeneous tumor

Fig. 7.1 Diagrammatic representation of stochastic and hierarchical models of tumor progression.
NSC normal stem cells; CSC cancer stem cells; CPC cancer progenitor cells/transiently amplifying
cells; TDC terminally differentiated cells; mut genetic mutation

7 Glioblastoma Stem Cells and Their Microenvironment