Biomedical Engineering Reference
In-Depth Information
epithelium that is negative for epidermal markers such as keratin (K) 5 and 14
(Yang et al., 1999; Millis et al., 1999). Furthermore, p51/p63 was recently
demonstrated to maintain the immaturity of keratinocytes stem cells by inhibit-
ing Notch1 activity (Okuyama et al., 2007).
2 Cancer Stem Cells and Stemness Signature in the Skin
Many studies performed over the past 30 to 40 years have shown that the
characteristics of stem cell systems, the specific stem cell properties described
for stem cells, are relevant to some forms of human cancer (Reya et al., 2001; Al-
Hajj et al., 2004; Fialkow et al., 1967; Hamburger and Salamon, 1977). Biolo-
gically distinct and relatively rare population of tumour-initiating cells have
been identified in cancers of the haematopoietic system, brain, breast, mela-
noma and other tumours (Lapidot et al., 1994; Bonnet and Dick, 1997; Singh
et al., 2004; Monzani et al., 2007; Al Hajj et al., 2003; Ignatova et al., 2002;
Singh et al., 2003; Galli et al., 2004). Cancer stem cells are defined as cells with
the capability of self-renewal, the potential to develop into any cell in the overall
tumour population and to proliferate driving the continued expansion of the
population of malignant cells (Fig. 2). Thereby, the properties of tumour-
initiating cells closely parallel the three features that define normal stem cells.
In fact both cells show the capability of asymmetric division into another stem
cell and one progenitor cell that further differentiate into mature progeny
comprising the adult tissue (Lajthe, 1979).
Regarding the origin of cancer stem cells, there are several lines of evidences
indicating that cancer stem cells can arise frommutated progenitor cells (Jamieson
et al., 2004; Cozzio et al., 2003; Huntly et al., 2004; Krivstov et al., 2006). However,
they might derive not only from stem cells pools but also from differentiated cells
that undergo transdifferentiation processes (Fig. 2). Although many tumours
contain cells that display stem cell-like features, the identity of the normal cells
that acquire the first genetic hits leading to the cancer-initiating cells remains
elusive (Perez-Osada and Balmain, 2003). The discovery that bone marrow-
derived stem cells home to sites of tissue damage opens up another possibility for
the origin of cancer stem cell (Borue et al., 2004; Brittan et al., 2005) (Fig. 2).
In the stem cell model the cancer disruption of genes involved in the regula-
tion of stem cell self-renewal seems to be important. It is thought that the
environment or the niche surrounding stem cells provides signals necessary
for the stem cells to continue to self-renew and upon exit from this niche the
stem cells begin to undergo differentiation (Spradling et al., 2001). The mechan-
ism by which stem cells decide to either remain in the niche or leave it could be a
major factor in the balancing act between stem cell self-renewal and differentia-
tion (Wallenfang and Matunis, 2003). In this connection, melanocyte growth
is under the control of keratinocytes and melanoma seems to escape from such
a control through different mechanisms such as downregulation of receptors
