Biomedical Engineering Reference
In-Depth Information
(Bainbridge, 1914), concluded, ''The congenital or embryonic theory of the
origin of cancer has received no support whatever from the experimental and
comparative investigations of recent times.'' In any case, physicians of that time
were overburdened with treatment of infectious diseases, such as tuberculosis
and syphilis, and there was no impetus to study cancer as there is today.
De-differentiation remained the dominant theory of the origin of cancer into
the 1980 s, despite observations on teratocarcinoma which proved that at least
this cancer, if not others, arose from stem cells and contained stem cells.
1.3 Teratocarcinoma, Stem Cells, and Cancer
Teratocarcinoma is a malignant cancer that arises from the germinal stem cells,
usually in the testes or the ovaries of a young adult (O'Hare, 1978). This cancer
usually grows rapidly, but responds well to therapy, as exemplified by the case
of Lance Armstrong. Studies beginning in the 1950 s on teratocarcinoma
proved not only that these cancers arise from stem cells, but also, more gen-
erally, that cancers contain stem cells, and that therapy can be directed against
these cancer stem cells.
1.3.1 Teratocarcinomas Contain Pluripotent Stem Cells
Barry Pierce and his colleagues (Pirece et al, 1978) demonstrated that terato-
carcinomas contain the same population of cells as is present in normal tissue:
stem cells, transit-amplifying cells, and differentiated cells. They demon-
strated that over 99% of the cells of most teratocarcinomas belong to mature
differentiated tissues, including derivative cells from all germ layers (skin,
glands, connective tissue, vessels, neural tissue, bone marrow, etc.) as well as
yolk sac and placental tissue (Pierce et al., 1978, 1960; Pierce and Dixon, 1959;
Pierce and Spears, 1988). In fact, the production and secretion of alpha-
fetoprotein (AFP) by the yolk sac component, and of chorionic gonadotropin
(CGH) by the placental component of teratocarcinomas, indicate that the
teratocarcinoma stem cells are totipotent, since they differentiate into cells
both of the body of the embryo and of the yolk sac and placenta. AFP and
CGH are considered to be oncodevelopmental markers; blood levels of these
markers are used for the diagnosis and follow-up of treatment of teratocarci-
nomas (Chan and Sell, 2001). The only malignant cells in the teratocarcinoma
are found in structures in the tumor that resemble early embryos (embryoid
bodies). In vitro culture or transplantation of teratocarcinomas to syngeneic
recipients can only be done using cells from the embryoid body (Pierce et al.,
1960). Therefore, the embryoid body cells possessed two classical properties of
cancer stem cells: the ability to grow in culture and the ability to initiate tumor
growth upon transplantation. Pierce's group concluded that cancers are
essentially caricatures of normal tissues (Pierce and Spears, 1988). They also
