Previous studies show that cancer-associated fibroblasts (CAFs) help cancer grow and spread, affecting patient outcomes. To develop better treatments, it’s crucial to understand how fibroblasts (FBs) turn into CAFs. The tumor microenvironment (TME) is like a chronic wound with ongoing inflammation, so FB activation in CAFs might be similar to FB activation in chronic inflammation. We suspected that the C/EBPβ protein, which increases in FBs during chronic inflammation, might also play a role in FB activation into CAFs.

This study aimed to explore the role of C/EBPβ in oxidative stress-related CAF transformation and its impact on colorectal cancer (CRC) progression. We used conditioned media (CM) from HCT116 CRC cells to activate CCD-18Co colon fibroblasts and assessed their ability to support HCT116 growth and spread using various assays. We also studied changes in the cytokine profile and oxidative stress of activated FBs.

Results showed that CM from HCT116 cells induced oxidative stress, changes in cytokine profile, CAF markers, and C/EBPβ expression in activated FBs. When oxidative stress was reduced, FAP and C/EBPβ expression decreased, and the FBs’ ability to support cancer progression was impaired. High C/EBPβ expression was linked to poor prognosis in CRC patients.

In conclusion, C/EBPβ plays a role in CAF transformation related to oxidative stress and could be a target for improving treatment outcomes in aggressive CRC.