Amanda Lund Lab

🔥 In our new BioRxiv preprint we show how cancer cell adaptations along a proliferation–robustness axis drive TME pro-tumor phenotypes. In this work, we asked whether cancer cell states are a result of a physiological response or adaptation to their microenvironment? To study this, we performed long-term (36 weeks) co-culture experiments with cancer cells evolving alongside continuously replenished fibroblasts or macrophages. This allowed us to distinguish between adaptive and physiological responses in specific cancer-TME interactions, which we then also recapitulated in patient tumors. We found that co-culture with fibroblasts induced the epithelial-mesenchymal transition in cancer cells and resulted in their increased drug tolerance, while co-culture with macrophages promoted stress, hypoxia responses and enhanced tumorigenicity. Adaptations were recurrent and partially reversible, but could not be explained by clonal selection, suggesting a dynamic non-mutational process. Moreover, adapted cancer cells elicited cell state changes in the fibroblasts and macrophages consistent with an extended phenotype mode of cancer evolution. Tremendous work by postdoctoral fellow Dr. Maayan Pour! biorxiv.org/content/10.64898…