Biomedical Engineering Reference
In-Depth Information
follicle gives rise to trichoepitheliomas, which vary in cellular differentiation but
usually contain both keratitic and basal regions, as well as clear cells character-
istic of hair follicle (Brown et al., 1998). Cells in the basal layer may give rise to
basal cell carcinomas or squamous cell carcinomas. Overexpression of Ras in
the more highly determined basal cells of the skin produces squamous cell
carcinoma (Waikel et al., 2001; Arnold and Watt, 2001), and induced expres-
sion of the c-myc gene in the non-proliferative suprabasal cells reactivates the
cell cycle and leads to hyperplasia (papillomas) (Pelengaris et al., 1999). Papil-
lomas do not progress to invasive tumors (Pelengaris et al., 1999). Examination
of the cell populations in skin cancer demonstrates that the malignant cells can
also differentiate, but that the proliferative transit-amplifying cells of the cancer
do not uniformly do so, unlike normal skin cells.
1.1.4 Malignant Cells May Become Benign
Pierce and Wallace (1971) published the results of an ingeniously simple experi-
ment demonstrating that the proliferating cells in a squamous cell carcinoma of
the skin can differentiate into non-proliferating terminally differentiated cells.
They pulse-labeled proliferating squamous cell carcinoma cells with tritiated
thymidine, which became incorporated into the newly formed DNA of cells
while they were in the process of division. When the cancers were examined
immediately after labeling, only the dividing cancer cells were labeled. How-
ever, when examined several days later, the terminally differentiated cells of the
cancer and even the keratin produced by the cancer contained the label. The
authors concluded that malignant cells can become benign. Thus, not all of the
cancer transit-amplifying cells divide symmetrically, giving rise to two continu-
ally proliferating transit-amplifying cells; instead some cancer transit-amplify-
ing cells divide asymmetrically, producing one daughter cell that remains a
transit-amplifying cell and one that terminally differentiates and sometimes to
two differentiating cells.
1.1.5 Comparison of Normal Tissue Renewal to Growth of Cancers
The difference between normal tissue renewal and cancer growth is that the
number of cells that are produced by cell division in normal tissue essentially
equals the number of cells that terminally differentiate in a given time period, so
that the total number of cells remains constant. In contrast, in cancers, the
proliferating transit-amplifying cells do not all terminally differentiate, and the
number of cells in the cancer increases (Sell and Pierce, 1994). The stem cells in
both normal tissue renewal and cancer growth consist of a small fraction of cells
that are not actively proliferating, and that fraction serves as a reserve cell
population. When a tissue stem cell divides, it gives rise to one daughter cell that
remains a stem cell and one daughter cell that begins the process of differentia-
tion by becoming a transit-amplifying cell (asymmetric division); thus, the stem
cells remain in the tissue for long periods of time, essentially the lifetime of the
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