Biomedical Engineering Reference
In-Depth Information
impair differentiation and to promote proliferation of the cells composing the
organizing structure of the niche. As such, studying those Wnt molecular events
is important to understand how their aberrant regulation leads to cancer
initiation and progression (Batlle et al., 2002), and this is certainly work in
progress. In conclusion, so far, matrix glycoproteins and the three-dimensional
spaces that they form are the ultrastructure of the stem cell niche. Secreted
proteins (by Wnt and other developmental pathways) offer a paracrine level of
control on the stem cells and the ultrastructure that holds them, playing a
crucial role in their cellular behavior and fate.
3.3 The Concept of Stem Cells and Cancer Stem Cells
Tumor tissue architecture shows many features of normal structures, with a
cellular hierarchy that regulates the balance between cell renewal and cell
differentiation. Interactions between cancer and stromal cells rely on deregu-
lated physiological feedback mechanisms that in normal circumstances are
responsible for tissue maintenance (Szabowski et al., 2000; Donjacour and
Cunha, 1991; Sternlicht et al., 1999; Muller et al., 2001). Normal stem cells
Fig. 2 Tissue homeostasis and carcinogenesis through stem cell cycling.
Quiescent stem cell (SC) with inactive Wnt: A. Upon tissue trauma, Wnt transduction leads to
activation of homeostatic SCs: B. These cells produce more pluripotent SCs as well as progeni-
tor cells with limited proliferative power: C that produce specialized differentiated cells (shown
in orange, purple,andblue) in order to regenerate the tissue. Upon repair, SCs cycle into a
quiescent state: D and A. Accumulation of oncogenic events may 'lock' activated SCs in a
permanent Wnt-driven state leading to cancer stem cells: E (Adapted from Beachy et al., 2004)
