Studying the Effect of Cancer-Associated-Fibroblasts on Colorectal Cancer Organoid Growth and Phenotype

Payton Noe

Document Type

Article

Publication Date

8-9-2024

Keywords

JGM

JAX Location

In: Student Reports, Summer 2024, The Jackson Laboratory

Abstract

Although human intestine in vitro models have shown significant progress in the field of biomedical engineering, they still lack the physiological components needed to study complex gut diseases such as colorectal cancer (CRC). Recent studies have attempted to mimic the CRC tumor microenvironment (TME) on a chip, discovering that cancer-associated fibroblasts (CAFs) increase the growth of patient derived tumor organoids (PDTOs), potentially influencing tumor response to therapy. This project aimed to further investigate the growth and advancement of CRC organoids in co-culture with CAFs and determine whether co-culturing with healthy adjacent fibroblasts can lead to the reversal of cancer or vice versa. To accomplish this, healthy and CRC organoid models were cultured alone and with healthy adjacent fibroblasts/CAFs. After 6 days of co-culture, the domes were fixed and processed _for immunofluorescence staining. Additionally, brightfield images of each dome were taken to assess differences in organoid morphology, size, and number. The results of these analyses indicate that CAFs may have a decreased ability to support healthy colon organoid growth when compared to CRC organoids. In the future, this experiment could be repeated to confirm these findings and better understand the mechanisms behind the observed growth differences.

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