Host: The Japanese Society of Toxicology
Colorectal cancer (CRC) organoids and paired cancer-associated fibroblasts (CAFs) from surgical specimens were established and we evaluated gene expression profiles of organoids with and without co-culture with CAFs. Original CRC showed variable expression profile for intestinal stem cell marker genes, e.g. LGR5, ORFM4. These characteristic gene expression patterns were maintained in each organoid model. On the other hand, we found that expression levels of several genes, which are substantially expressed in original CRC, were downregulated in organoids but reproduced by co-culturing with CAFs. They comprised immune response- and external stimulus-related genes, e.g.,REG family and dual oxidases (DUOXs), which are known to have malignant functions, leading tumor cells to proliferative and/or anti-apoptotic states and drug resistant phenotypes. In addition, the degree of differential induction of REG1 and DUOX2 in the co-culture system varied depending on CAFs from each CRC case.
In conclusion, CRC organoids co-cultured with CAF should be applied for basic and translational researches under partially reproduced tumor-microenvironment.
