Investigating the Role of Inflammatory Markers in Colitis-Associated Colorectal Cancer Development Using the AOM/DSS Mouse Model
Master thesis
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https://hdl.handle.net/11250/3157957Utgivelsesdato
2024Metadata
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Sammendrag
Background: Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD). The AOM/DSS murine model, which closely mimics the development of human CAC, was employed to induce colorectal cancer in A/J mice. This study aimed to investigate the relationship between inflammatory markers and the development of CAC.
Methods: A/J mice were subjected to 1, 2, or 3 cycles of DSS treatment and recovery periods. Tumor burden, flat aberrant crypt foci (fACF) development, and levels of acute-phase proteins (SAP, CRP, Haptoglobin) and cytokines (TGF-β, TNF-α, IL-6, IL-10, IL-13, IL17/IL-17A, and IFN- γ) were assessed using multiplex assays. The gene expression of TNF-α and GAPDH was analyzed by qPCR.
Results: The group exposed to three DSS cycles and an extended recovery period of 3 weeks exhibited the highest tumor burden, underscoring the critical role of inflammation in tumor progression. However, fACF analysis revealed no significant differences between experimental groups, suggesting that repeated DSS exposure may not substantially influence the development of fACF beyond the initial AOM injection. The observation of an increase in total lesion number in groups receiving multiple DSS cycles, coupled with the understanding that DSS induces inflammation and DNA damage, suggests a potential role for DSS in promoting the formation of new fACF, warranting further investigation into the dynamics of fACF development in the AOM/DSS model. SAP levels were significantly elevated in the group receiving two DSS cycles, potentially serving as a marker for monitoring acute inflammation in the AOM/DSS model. The lack of detectable levels of several cytokines and the absence of significant differences in TNF-α expression levels suggest that these might not be primary drivers of inflammation or tumorigenesis in this specific model.
Conclusion: This study highlights the complex interplay between inflammation and colorectal cancer, emphasizing the need for further research to elucidate the underlying mechanisms and identify potential therapeutic targets. Future studies could benefit from employing longitudinal study designs and incorporating a wider range of inflammatory markers to better understand the complex relationship between inflammation and colorectal cancer. The inclusion of robust control groups and the analysis of multiple organs will further enhance our understanding, ultimately leading to the development of new preventive and therapeutic strategies.