Tumour cell heterogeneity directs fibroblast phenotypes and reciprocal signalling

Using an in vitro model of intra-tumoral heterogeneity we find that phenotypically diverse tumour cell clones establish unique interactions with stromal fibroblasts. Clonal tumour cell populations induce distinct phenotypic traits in co-cultured fibroblasts. Reciprocally, tumour cell clones exhibit a distinct transcriptional response to stromal co-culture, increasing their phenotypic diversity. Our data suggest that local interactions between tumour cell clones and stromal fibroblasts act to establish dynamic micro-niches, which increase tumour cell operational space to bypass therapeutic interventions.