KEY TAKEAWAYS
- The study aimed to investigate the role of MMP11 in TME and its mechanism in CRC.
- The results showed that MMP11 expression was elevated in CRC and correlated with poorer survival, promoting cell migration and invasion by elevating Slug protein.
Matrix metalloproteinase-11 (MMP11), a protein involved in the breakdown of the extracellular matrix, has been implicated in colorectal cancer (CRC) progression. However, its specific role in the tumor microenvironment (TME) and its underlying mechanisms remain unclear.
Chaomin Pan and the team aimed to explore the impact of MMP11 on CRC progression, particularly its influence on the TME and its mechanism of action.
Researchers employed a combination of in vitro and clinical methods to assess the impact of MMP11 knockdown on CRC cell lines (RKO and SW480). They used Western blot and qRT-PCR to measure changes in protein and mRNA expression levels, transwell assays to evaluate cell migration and invasion, and immunohistochemistry to examine MMP11 expression in CRC tissues and its association with clinicopathological features. Additionally, they analyzed MMP11 expression in relation to patient age, tumor stage, and survival.
The results revealed that MMP11 mRNA expression was significantly higher in CRC cells compared to normal cells and was stimulated in CCD-18Co fibroblasts. MMP11 levels were elevated in individuals aged 65 years or younger, those in the T4/T3 group, and Stage III/IV patients.
Overall and disease-free survival (DFS) rates differed significantly between high and low MMP11 expression groups. ROC curves for MMP11 at 1, 3, and 5 years were 0.450, 0.552, and 0.560, respectively. MMP11 promoted CRC cell migration and invasion by increasing Slug protein expression.
Additionally, MMP11 was positively associated with M0-macrophages and negatively associated with M1-macrophages, activated NK cells, resting NK cells, activated CD4 memory T cells, and follicular helper T cells, highlighting its significant interactions with tumor immunology.
The study concluded that MMP11 plays a crucial role in CRC development, likely by increasing cell migration and invasion, possibly through Slug protein elevation. Furthermore, MMP11 exhibited significant interactions with the tumor immune landscape, which warrants further investigation.
This work was supported by the Basic and Applied Basic Research Fund of Guangdong Province (grant number 2019A1515110078), the National Nature Foundation Youth Program (grant number 12026605), the Guangdong Province Basic and Applied Basic Research Fund Project Regional Joint Fund-Youth Fund Project (2020A1515110359), the Guangdong Medical Science and Technology Research Fund (A2020133), and the Presidential Foundation of Southern Medical University Southern Hospital (2023A043).
Source: https://pubmed.ncbi.nlm.nih.gov/39239548/
Pan C, Dai J, Wei Y, et al. (2024). “Matrix Metalloproteinase 11 Promotes Migration and Invasion of Colorectal Cancer by Elevating Slug Protein.” Int J Med Sci. 2024;21(11):2170-2188. Published 2024 Aug 13. doi:10.7150/ijms.98007
