Abstract/Summary

Cancer is a disease of evolution. Mutations within a cell lead to the acquisition of cancerous phenotypes. Tumour evolution depends on heritable differences between cells. The extent of heritable variation has not been measured for any trait in cancer cellpopulations. In this thesis techniques have been developed to estimate the broad-sense heritability (H2) of cancer cell traits in vitroand usedto estimate the H2of cell motility. Cell motility is a trait related to the cancer hallmark of metastasis. Results showthat motility is strongly heritable with H2values ranging from 0.77-0.36 across multiple cell generations. H2estimates appeared to decrease slightly between more distantly related cells, a trend that could occur due to a decrease in the genetic contribution to motility or an increase in environmental variation. This was tested by treating cells with epigenetic inhibitors and obtaining H2 estimates.Results showed H2estimates were not significantly affected by the application of epigenetic inhibitorswith values ranging from 0.95-0.18.Quantification of the amount of environmental variation in in vitrocell culture media was attempted using image analysis of fluorescent particles. Variation in particle distribution was found at a range of concentrations, nM –mM. Direct quantitative measures of evolvability in cell traits could have valuable applications to cancer research and tumour treatment.To understand tumour progression, evolutionary theory can be applied to cancer cells in vitroto elucidate the selective pressures driving the evolution of cancer cell traits. In this project experimental evolution techniques have been adapted from microbiology and applied to cancer cell linesin vitro. Adaptation of cell lines to lownutrient environments over 12 weeks showed dispersal theory may play a role in the selection of the cancer cell trait motility. Understanding the selective pressures driving the acquisition of cancer phenotypes will have valuable applications clinically inunderstandingtumour progression.