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 X. Sun,
Heinz-Josef Lenz,
Jonathan E. Katz,
Shannon M. Mumenthaler
Affiliations
Carly Strelez
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Sujatha Chilakala
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Kimya Ghaffarian
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Roy Lau
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Erin Spiller
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Nolan Ung
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Danielle Hixon
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Ah Young Yoon
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Ren X. Sun
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Heinz-Josef Lenz
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Jonathan E. Katz
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA
Shannon M. Mumenthaler
Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA 90064, USA; Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Corresponding author
Summary: Colorectal cancer (CRC) progression is a complex process that is not well understood. We describe an in vitro organ-on-chip model that emulates in vivo 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.
