Colorectal cancer organoids for the analysis of fibroblast-tumor cell interactions
2023
Semmelweis University, Budapest, Hungary
Colorectal cancer (CRC) is a common disease and a leading cause of cancer-related deaths. An accumulation of cancer-associated fibroblasts (CAFs) causes tumor cells to become more aggressive and behave like stem cells, which indicates a poor prognosis. To explore the role of CAFs and potential treatments, this study used a patient-derived organoid model of CRC. Fibroblasts from tumor tissue of CRC patients were isolated and cultured together with the CRC organoids to analyse how these cells interact.
Using these organoid-based experiments, fibroblasts that produce high levels of the protein CD142 were identified. These fibroblasts stimulate the growth of CRC cells more than fibroblasts that produce low levels of CD142. They do this by releasing more of a growth factor called HGF. The effect of different combinations of cancer drugs on the cancer cells within the organoids was also studied. It was shown that a drug that inhibits the protein HSP90, namely PU-H71, mainly affected the CD142-producing fibroblasts. Both the cancer cells and the CAFs were sensitive to a drug that inhibits the protein BCL-XL, namely A-1155463 (BCLi).
The results from the organoid experiments suggest that the drugs A-1155463 (BCLi) and PU-H71 could be used to destroy cancer cells and reduce the number of CD142-producing CAFs that promote tumor growth. The use of CRC organoids made it possible to develop a strategy that aims to treat both cancer cells and stromal fibroblasts at the same time to prevent tumors from growing back.
High CD142 level marks tumor-promoting fibroblasts with targeting potential in colorectal cancer
Zoltán Wiener
Added on: 05-12-2025
[1] https://www.mdpi.com/1422-0067/24/14/11585
