Epithelial tissue architecture protects against cancer.
We consider the design of colon crypts from the point of view of minimizing the likelihood of generation of cancerous mutations. A stochastic mathematical model (a finite branching process) is developed and fully analyzed. It is found that depending on the mutation rates, different designs are evolutionarily advantageous. If the mutation rates associated with stem cells are a lot higher than the mutation rates of daughter cells, then few stem cells per crypt is the evolutionarily optimal strategy. If the mutation rates of stem cells are of the same order of magnitude or lower than those for daughter cells, then having as many stem cells per crypt as possible is the desirable design. We also found that the optimal evolutionary strategy may work very well to protect the organism from cancer in the young age, but the same strategy becomes detrimental as the organism ages. It pushes the onset of cancer back in time, but it results in an elevated cancer initiation rates as the organism gets older. Our model quantifies the idea that cancer and aging are the two sides of one coin.
Komarova
Natalia L
NL
Department of Mathematics, University of California - Irvine, Irvine, CA 92697, United States; Department of Ecology and Evolution, University of California - Irvine, Irvine, CA 92697, United States. Electronic address: komarova@math.uci.edu.
Myint
Philip C
PC
Department of Ecology and Evolution, University of California - Irvine, Irvine, CA 92697, United States.
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000465:Algorithms; D000818:Animals; D049109:Cell Proliferation; D043171:Chromosomal Instability / Q000235:genetics; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D003198:Computer Simulation; D019143:Evolution, Molecular; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011336:Probability; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D013269:Stochastic Processes
D025601:Adenomatous Polyposis Coli Protein