Cell News 4/2014
19
Research news
layer (Koster 2010) (fig. 1B). Different stem and progenitor cells
located in the basal layer of the IFE and in specific areas of hair
follicles guarantee constant self-renewal during homeostasis or
in case of injury (Blanpain and Fuchs 2014; Watt and Jensen
2009). The stratifying epidermis is not a classically polarized
epithelium with apico-basal polarity on a cellular level. Instead,
it establishes polarity along the basal to apical axis of the tissue,
with the stratum granulosum forming the viable apical bound-
ary (Niessen et al. 2012). Functional tight junctions are found
in the second-last viable layer (Yoshida et al. 2013) (fig. 1B)
and, as in simple epithelia, may serve as a fence necessary for
restricting ‘apical’ targeting of protein and lipid vesicles at the
transition between the granular and cornified layer.
Importantly, despite a variety of repair mechanisms, the epider-
mis is prone to formation of different tumors, such as melano-
ma, basal cell carcinoma, squamous cell carcinoma and keratoa-
canthoma, which can be caused by UV radiation, chemicals and
pathogens as well as hereditary factors. Most human cancers
are of epithelial origin, and non-melanoma skin cancer reflect
the most frequent cancer in humans.
Epithelial cell polarity, growth control and cancer
In complex organisms, tissue homeostasis requires the coordina-
tion of self-renewal, differentiation and elimination of damaged
cells while the overall tissue function is preserved. Disturbances
in tissue homeostasis may result in a failure to repair and renew
and subsequent degeneration, or in hyperplastic growth and de-
velopment of cancer. In epithelial cells, the establishment of cell
polarity is coordinated with cellular growth control, and growth
is inhibited once cells reach a critical density that is sensed
by molecules of intercellular adhesions (McClatchey and Yap
2012). When cell polarity is disrupted, cells may become insen-
sitive to growth inhibition, favoring neoplasia. The initiation and
progression of cancer are characterized by unrestricted growth
and a gain of metastatic capacity, accompanied by changes in
the cyto-architecture of cells (Hanahan et al. 2000). Work in
Drosophila, mammalian cell cultures and mouse models show-
Figure 2:
In vivo
mouse model to mimic Ras-mediated non-melanoma skin cancer.
A, Schematic representation of two-stage DMBA/TPA skin carcinogenesis model. After dorsal shaving, DMBA is once topically applied to 8week-old mice,
followed by repeated TPA applications (20x) twice a week.
B, Examples of skin tumors developed in mice in the course of two-stage DMBA/TPA skin carcinogenesis. H&E cross sections. DMBA, 7,12-dimethylbenz(a)
anthracene; TPA, 12-O- tetradecanoylphorbol-13-acetate. Left: overview of four different tumor types; right: examples of local invasion of tumor cells
derived from tumors shown left.
