Minimizing the risk of cancer: tissue architecture and cellular replication limits

Normal somatic cells are capable of only a limited number of divisions, which prevents unlimited cell proliferation and the onset of tumours. Cancer cells find ways to circumvent this obstacle, typically by expressing the enzyme telomerase and less often by alternative recombination strategies. Given this fundamental link between cellular replication limits and cancer, it is important to understand how a tissue's architecture affects the replicative capacity of a cell population. We define this as the average number of remaining divisions at equilibrium. The lower the replication capacity, the lower the chances to escape the replication limit during abnormal growth when a tumour develops. In this paper, we examine how the replication capacity is influenced by defining characteristics of cell lineages, such as the number of intermediate cell compartments, self-renewal capability of cells and division rates. We describe an optimal tissue architecture that minimizes the replication capacity of dividing cells and thus the risk of cancer. Interestingly, some of the features that define an optimal tissue architecture have been documented in a variety of tissues, suggesting that they may have evolved as a cancer-protecting strategy in multicellular organisms.