Biomedical Engineering Reference
In-Depth Information
organism. The number of cells in a cancer increases with time, because the
transit-amplifying cells give rise to two cells that do not mature and retain the
potential to divide (symmetric division) or the mature cells do not die or both.
1.1.6 Normal Tissue Contains Stem Cells with Malignant Potential
Attempts to culture cells from normal tissues and cancers were well underway in
the 1950 s (see below), and there were even some early studies suggesting that
normal tissues contain stem cells with malignant potential. For example, in
1953, Harry Goldblatt, better known for his studies on renal hypertension
(Goldblatt et al., 1934), found that malignant cells could be derived from
normal rat myocardium (fibroblasts) if the cells were cultured for a long time
in anaerobic conditions (Goldblatt and Cameron, 1954). Most normal tissue
cells do not survive under these conditions. He and his co-worker suggested that
normal tissue contains rare cells (stem cells?) with the potential for malignant
change under selected culture conditions. On page 526 of their paper, they
wrote, ''It seems possible that in all embryonic, and even adult, normal tissues
there may be scattered cells, or groups of cells of potentially neoplastic sort,
which naturally possess the ability to use the fermentative, glycolytic mechan-
ism, at least under anaerobic conditions, and that repeated, brief exposure of
cultures of normal tissue containing such cells to an atmosphere deprived of
oxygen, alternating with long periods when adequate oxygen is available, thus
permitting recovery, might favor their multiplication and even interfere with the
growth of the regional, normal cells.'' Given the previous observations of Otto
Warburg and associates (Warburg et al., 1927) that a common feature between
cancer cells and embryonic cells is the ability to use glycolytic metabolism, the
implication is that normal tissues contain stem cells that retain the properties of
embryonic stem cells, and that such cells can become malignant under selective
growth conditions.
1.2 Theories of the Cellular Origin of Cancer
Two major theories of the origin of cancer have vied for acceptance in modern
cellular biology: origin from stem cells and origin via de-differentiation of
mature cells.
1.2.1 Embryonal Rest Theory of Cancer
The concept that cancers arise from stem cells in adult tissues was originally
formulated as the embryonal rest theory of cancer. The first known theory of
cancer proposed by Hippocrates, Celsus, and Galen was that cancer is caused
by an excess of black bile, according to the humoral theory of disease (Shimkin,
1977). However,
in the early and mid-1800 s, with the invention of the
