Clonal cooperation through soluble metabolite exchange facilitates metastatic outgrowth by modulating Allee effect.

ABSTRACT: Cancers feature substantial intratumoral heterogeneity of genetic and phenotypically distinct lineages. Although interactions between coexisting lineages are emerging as a potential contributor to tumor evolution, the extent and nature of these interactions remain largely unknown. We postulated that tumors develop ecological interactions that sustain diversity and facilitate metastasis. Using a combination of fluorescent barcoding, mathematical modeling, metabolic analysis, and in vivo models, we show that the Allee effect, i.e., growth dependency on population size, is a feature of tumor lineages and that cooperative ecological interactions between lineages alleviate the Allee barriers to growth in a model of triple-negative breast cancer. Soluble metabolite exchange formed the basis for

SUBMITTER: Hershey BJ 

PROVIDER: S-EPMC10881076 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature