Page 285 - 20dynamics of cancer

270 CHAPTER 12

perhaps one step along in carcinogenesis, cannot normally expand be-
yond its compartmental boundaries, thus limiting the target number of
cells for the accumulation of subsequent mutations.
Cairns (1975) pointed out that each tissue probably has different rules
governing the territoriality of proliferating cells. Those spatial rules de-
termine which kinds of variant cell succeed in each type of tissue. Those
variants that could break territorial boundaries and invade neighboring
compartments would gain a significant competitive advantage, increase
their populations, and provide a large clonal target for subsequent ad-
vances in progression.
Repression of competition has become an important general concept
in the study of cooperative evolution (Buss 1987; Frank 1995; May-
nard Smith and Szathmary 1995; Frank 2003a). Perhaps such repres-
sion was an essential step in the evolution of complex multicellularity,
in which large populations of independent cells act in a mostly cooper-
ative manner.

12.6 Summary

This chapter reviewed the processes of tissue renewal. Most renew-
ing tissues derive from a small number of stem cells. Mutations to stem
cells pose the main risk for cancer. Stem cells may have various mech-
anisms to reduce their mutation rate. For example, the stem lineage
may retain the DNA template and segregate new copies of the DNA to
the daughter cells in the transit lineage. In addition, the patterns of
tissue renewal from stem cells and the shape of stem cell lineages af-
fect the accumulation of somatic mutations. To analyze in more detail
how somatic mutations accumulate, I discuss in the next chapter the
population genetics of somatic cell lineages.