A Window into Colorectal Cancer: Novel Tumor-on-Chip Model Combined with High-Content Imaging Offers Insight into Colorectal Cancer


Colorectal cancer (CRC) is one of the deadliest cancers in the U.S., yet we still understand very little about the mechanisms behind this disease. We are developing a CRC Tumor-Chip model that can recapitulate the complex nature of tumorigenesis in order to increase our understanding of CRC and accelerate the discovery of effective new treatments.

The Organs-on-Chips technology maintains physiologically relevant aspects of organ structure and function by incorporating tissue compartments and mechanical forces to recreate in vivo mechanical forces (peristalsis) and fluid flow. The Intestine-Chip consists of two fluidic channels (endothelial cells and colon epithelial cells) separated by a porous membrane. We introduced fluorescently-labeled CRC cell lines onto the epithelium through optimization of seeding densities and culture conditions. CRC cells grew as 3-D clusters of varying sizes when seeded on the Chips compared to the 2-D elongated morphology traditionally observed in monolayer cultures.

CRC Tumor-Chip model presents a challenge in assessing and quantifying cellular behaviors in response to perturbations to the system. To overcome this hurdle, we utilized a high-content imaging platform to quantify tumor cells within this heterocellular environment. Using this method, cancer cell growth was assessed and compared to traditional 2-D cell culture methods. Not surprisingly, CRC cells grew slower on the Chip than in conventional monolayer.