Human Colorectal Cancer-on-chip Model to Study the Microenvironmental Influence on Early Metastatic Spread

Overview

Journal iScience

Publisher Cell Press

Date 2021 Jun 11

PMID 34113836

Citations 26

Authors

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

Soon will be listed here.

Abstract

Colorectal cancer (CRC) progression is a complex process that is not well understood. We describe an organ-on-chip model that emulates 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.

Citing Articles

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