摘要：SummaryColorectal cancer (CRC) progression is a complex process that is not well understood. We describe anin vitroorgan-on-chip model that emulatesin vivotissue structure and the tumor microenvironment (TME) to better understand intravasation, an early step in metastasis. The CRC-on-chip incorporates fluid flow and peristalsis-like cyclic stretching and consists of endothelial and epithelial compartments, separated by a porous membrane. On-chip imaging and effluent analyses are used to interrogate CRC progression and the resulting cellular heterogeneity. Mass spectrometry-based metabolite profiles are indicative of a CRC disease state. Tumor cells intravasate from the epithelial channel to the endothelial channel, revealing differences in invasion between aggressive and non-aggressive tumor cells. Tuning the TME by peristalsis-like mechanical forces, the epithelial:endothelial interface, and the addition of fibroblasts influences the invasive capabilities of tumor cells. The CRC-on-chip is a tunable human-relevant model system and a valuable tool to study early invasive events in cancer.Graphical abstractDisplay OmittedHighlights•A human colorectal cancer chip recapitulates aspects of CRC biology•On-chip imaging and metabolomic effluent analyses offer insight into progression•Organ-on-chip conditions induce phenotypic heterogeneity compared to 2D cultures•Stromal cell cross talk and mechanical forces increase tumor cell intravasationClassification Description: Bioengineering; Tissue engineering; Cancer; Biomedical materials
