Biomedical Engineering Reference
In-Depth Information
Stem Cells and Cancer: An Introduction
Stewart Sell
Abstract Cancer tissue contains the same cell populations as do normal adult
tissues: stem cells, proliferating transit-amplifying cells, terminally differen-
tiated (mature cells) and dead cells. However, the cancer transit-amplifying
cells are arrested at a stage of maturation where many of the transit-amplifying
cells continue to divide and do not die. During normal tissue renewal, the
transit-amplifying cells produce progeny that differentiate and die. Because of
this difference, cells in a cancer continue to accumulate. On the other hand, the
number of dividing cells in normal tissue essentially equals the number of
differentiating cells, so that the total number of cells remains relatively
constant.
The idea that cancer arises from stem cells was first proposed over 150 years
ago as the embryonal rest theory of cancer. However, by the beginning of the
20 th century, the embryonal rest theory of cancer was discarded, and the
hypothesis that cancer arises from de-differentiation became generally
accepted. Then, about 50 years ago, studies on cancers of germinal cells (ter-
atocarcinomas) re-established the principles that cancer arises from stem cells,
that cancers contain stem cells, and that cancer could be treated by induction of
differentiation (differentiation therapy). However, teratocarcinomas were con-
sidered exceptions to the rule, and the de-differentiation theory of origin
remained generally accepted for most cancers until the 1980 s. Then studies on
the cellular origin of cancer during experimental chemical hepatocarcinogenesis
showed that hepatocellular cancer did not arise from de-differentiation of
hepatocytes, as was generally believed, but rather from maturation arrest of
cell in the hepatocyte lineage. The re-emergence of the stem cell theory of cancer
preceded the current excitement in cancer stem cells.
Over the last 10 years, differentiation therapy has been applied with great
success to cancer of the blood cells (leukemias) by inactivation of the signaling
pathways that allow the leukemic transit-amplifying cells to continue to
S. Sell (*)
New York State Health Department, Wadsworth Center, P.O. Box 509, Room C-551,
Empire State Plaza, Albany, NY 12201, USA
