Differential gene expressions of cancer cells cultured in an oxygen-limiting, micro-metabolic rewiring (μMeRe) device over their normoxia control

Cancer metabolism plays an essential role in therapeutic resistance, where significant inter- and intra-tumoral heterogeneity exists. Hypoxia is a prominent driver of metabolic rewiring behaviors and drug responses. Recapitulating the hypoxic landscape in tumor microenvironment thus offers unique insights into heterogeneity in metabolic rewiring and therapeutic responses, to inform better treatment strategies. We developed a micro-metabolic rewiring (μMeRe) device that provides the scalability and resolution needed to characterize the metabolic rewiring behaviors of different cancer cells in the context of hypoxic solid tumors. Our device generates hypoxia through cellular metabolism without external gas controls, enabling the characterization of cell-specific intrinsic ability to drive hypoxia and undergo metabolic rewiring. We assessed the changes in the transcriptomic profile of different cancer cells in the μMeRe device compared to their normoxia counterpart through bulk RNA-seq. Our data confirms heterogeneity and commonality of rewiring behaviors of diverse cancer cell types.