Human colorectal cancer-on-chip model to study the microenvironmental influence on early metastatic spread.

IScience
Carly StrelezShannon M Mumenthaler

Abstract

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.

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Software Mentioned

Ingenuity Pathway Analysis ( IPA )
Elmer Harmony
Mass Profiler Professional ( MPP )
Harmony
Profinder
Ingenuity Pathway Analysis ( IPA
Imaris
GraphPad Prism
Emulate
IPA

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