Biomedical Engineering Reference
In-Depth Information
regulation of the epigenetic control of expression, disable key nodes in the net-
works controlling cell growth and differentiation. The rate of mutation can be
increased by failure to maintain genetic integrity. This failure results in genetic
instability caused either by deficiencies in the DNA repair machinery or by
chromosomal instability. Defects in DNA repair can cause inherited susceptibil-
ity for certain cancers in humans, and chromosomal instability, manifested by
loss of heterozygosity, is commonly observed in human cancerous tissue (5).
The search for the genes responsible for chromosomal instability is being very
actively pursued, and their identification will elucidate both how their products
function and the role they play in tumor formation and progression (6,7).
Clonal evolution has been and continues to be regarded as the principal
mechanism underlying tumor formation and progression (8). Implicit in the
microevolutionary view of these processes is the notion of competition between
the variants generated by mutation. Selection, playing on a checkerboard of
mutations, can be a factor determining the particular genotype realized in a
tumor cell population. Thus, the ecology of cancer cell populations that
constitute the tumoral tissue is likely to depart significantly from that observed
in normal tissues.
2.
POPULATION DYNAMICS
Under a population-based view, two leading processes exploit mutational
events: competition among different clones and expansion of those with larger
growth rates. By applying the standard theory of ecological competition (9,10),
coexistence is allowed by a limited range of conditions, defined by the strength
of the interspecific interactions. Given two distinct populations, both will be
present at low competition rates. Otherwise, one of the populations will win and
exclude the second one. Thus, unless the parameters that define competition are
properly tuned to avoid the parameter range of competitive exclusion, the popu-
lation will tend to homogeneity.
Recent progress in the area of spatial ecology supports the idea that hetero-
geneity may be much more common than predicted by competition theory.
Competitors that may exclude each other under defined experimental conditions
may coexist under a spatially explicit framework (11,12). This is largely a con-
sequence of the constraints imposed by space under limited dispersal. If two
species that are good competitors involve individuals with short-range move-
ment, the fact that their direct impact on other individuals is limited to their
nearest neighbors slows down or even cancels the expected effects of exclusion.
The final result of this spatially extended competition scenario is a patchy distri-
bution of the two species that can be generalized to many different coexisting
species. This occurs under a wide range of conditions, and it is not the result of a
specific choice in the model (13,14). The only requirement is that spatial effects
