Variation in the life history strategy underlies functional diversity of tumors.

Abstract

Classical r- vs. K-selection theory describes the trade-offs between high reproductive output and competitiveness and guides research in evolutionary ecology. While its impact has waned in the recent past, cancer evolution may rekindle it. Herein, we impose r- or K-selection on cancer cell lines to obtain strongly proliferative r cells and highly competitive K cells to test ideas on life-history strategy evolution. RNA-seq indicates that the trade-offs are associated with distinct expression of genes involved in the cell cycle, adhesion, apoptosis, and contact inhibition. Both empirical observations and simulations based on an ecological competition model show that the trade-off between cell proliferation and competitiveness can evolve adaptively. When the r and K cells are mixed, they exhibit strikingly different spatial and temporal distributions. Due to this niche separation, the fitness of the entire tumor increases. The contrasting selective pressure may operate in a realistic ecological setting of actual tumors.