Integrating Ecology and Cancer: Investigations in a Prostate Cancer Cell Model

Evolution and ecology can be used to gain a better understanding of cancer. Here, my focus is on applying concepts and tools from evolution and ecology to generate new insights into the importance of the tumor microenvironment and tumor heterogeneity for cancer progression. I used a model prostate cancer cell line called PC-3, which contains both an epithelial cell type (PC-3E) and a mesenchymal cell type (TEM4-18) that are maintained at about a 75:25 PC3E:TEM4-18 ratio in the parental population. Mesenchymal cells are particularly interesting because they have the ability to metastasize. Data of the growth rates of each cell type in isolation suggested that PC-3E cells have a higher growth rate than the TEM4-18 cells. Because of this, it unclear what mechanisms maintain the TEM4-18 cells in the parental population. To begin to understand how the dangerous mesenchymal cells are maintained, I combined the PC3E and TEM4-18 cells at equal proportions in one flask and monitored the population for 6 weeks, noting how the proportions of each cell type changed as the experiment progressed. The experiment resulted in the mesenchymal cells depleting rapidly from the population. We next combined the mesenchymal population with the parental population in equal proportions and performed the experiment again. We found that, rather than depleting rapidly as they did with the epithelial cells, the mesenchymal cells were maintained in the population for the duration of the experiment. This result was striking because the composition of the parental cell line should be very similar to the composition of a combined population of PC-3 and TEM4-18 cells. Finally, we cultured each cell type in isolation and compared the growth rates obtained from these experiments to the growth rates found in the experiments with two combined cell types. While the mesenchymal and epithelial cell types had similar growth rates in all conditions, the parental cells had different growth rates when cultured alone vs. when cultured with another cell line. We concluded that the different proliferative success of the TEM4-18 cells in the different environments was likely due to microenvironmental differences between the parental cell line and the PC-3E + TEM4-18 combination. This research integrates the ideas of evolution and cancer to gain an understanding of metastatic cells. An evolutionary approach is especially powerful in the wake of growing knowledge of tumor heterogeneity and the tumor microenvironment, and may lead to novel methods of treating cancer.