Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread
Carly Strelez, Sujatha Chilakala, Kimya Ghaffarian, Roy Lau, Erin Spiller, Nolan Ung, Danielle Hixon, Ah Young Yoon, Ren Sun, Heinz‐Josef Lenz, Jonathan E. Katz, Shannon M. Mumenthaler
Abstract
tissue 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.