Competition and niche construction in a model of cancer metastasis.

Jimmy J Qian,Erol Akçay,Zhiqian Zhang

doi:10.1371/journal.pone.0198163

Abstract

Niche construction theory states that not only does the environment act on populations to generate Darwinian selection, but organisms reciprocally modify the environment and the sources of natural selection. Cancer cells participate in niche construction as they alter their microenvironments and create pre-metastatic niches; in fact, metastasis is a product of niche construction. Here, we present a mathematical model of niche construction and metastasis. Our model contains producers, which pay a cost to contribute to niche construction that benefits all tumor cells, and cheaters, which reap the benefits without paying the cost. We derive expressions for the conditions necessary for metastasis, showing that the establishment of a mutant lineage that promotes metastasis depends on niche construction specificity and strength of interclonal competition. We identify a tension between the arrival and invasion of metastasis-promoting mutants, where tumors composed only of cheaters remain small but are susceptible to invasion whereas larger tumors containing producers may be unable to facilitate metastasis depending on the level of niche construction specificity. Our results indicate that even if metastatic subclones arise through mutation, metastasis may be hindered by interclonal competition, providing a potential explanation for recent surprising findings that most metastases are derived from early mutants in primary tumors.

Highlights

A cancer tumor is a collection of abnormal cells whose unregulated proliferation damages surrounding host tissue, often resulting in patient death
The conditions for metastasis are equivalent to the invasion conditions of secondary or global producers into this tumor, since pre-metastatic niche construction is required for circulating tumor cells to settle into a secondary site
We presented a simple model of niche construction in cancer, where local niche construction benefits all primary tumor cells by increasing the carrying capacity, and secondary niche construction is needed for successful metastasis

Summary

Introduction

A cancer tumor is a collection of abnormal cells whose unregulated proliferation damages surrounding host tissue, often resulting in patient death. It is a population of genetically and phenotypically diverse cells that compete, propagate, and contribute (or not) to the cellular society. The evolutionary dynamics of tumors are only fully comprehensible when the ecological context—the tumor ecosystem—is considered [1, 2] This entails applying ecological concepts such as predation, niches, and invasion (in evolutionary theory and in this paper, “invasion” refers to the establishment of a mutant genotype into an existing population, a concept distinct from cancer “invasion,” or expansion, into surrounding tissue)

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Conclusion