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CD147 and matrix-metalloproteinase-2 expression in metastatic and non-metastatic uveal melanomas
Julia Lüke1, Vlatka Vukoja2, Tim Brandenbusch2
1Department of Ophthalmology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany. Julia.lueke@uk-sh.de1.
Background:
Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis.
Methods:
The expression of CD147 and MMP-2 was analyzed in 49 samples of uveal melanomas. Triple immunofluorescence stainings using markers against glial cells (GFAP), endothelial cells (CD34) and macrophages (CD68) were performed to further analyse the exact localisation of CD147 and MMP-2 positivity. In 28 cases clinical metastatic disease were found. The remaining 21 cases showed no signs of metastatic disease for an average follow-up of 10 years. Correlation analysis (Pearson correlation) was performed to analyse the association of CD147 and MMP-2 expression with known prognostic factors, vasculogenic mimicry (VM), the mature vasculature (von Willebrand Factor) and tumor induced angiogenesis (by means of Endoglin expression).
Results:
CD147 and MMP-2 were expressed in 47 (96.0 %) of the uveal melanomas. CD147 up-regulation was significantly correlated with a higher MMP-2 expression. The overall expression analysis revealed no significant difference in the metastatic (p = 0.777) and non-metastatic subgroup (p = 0.585). No correlation of CD147 expression and any system of blood supply was evident. In the non-metastatic sub-group a significant correlation of clustered CD147 positive cells with largest basal diameter (p = 0.039), height (p = 0.047) and TNM-stage (p = 0.013) was evident.
Conclusions:
These data may indicate that CD147 regulates MMP-2 expression in uveal melanoma cells.
Insights
Matrix-metalloproteinase (MMP) inducer CD147 may regulate MMP-2 expression in uveal melanoma cells. This study found CD147 up-regulation correlated with higher MMP-2 expression but not overall metastasis.
Area of Science:
- Ophthalmology
- Oncology
- Molecular Biology
Background:
- Extracellular matrix remodeling, driven by matrix-metalloproteinase (MMP) inducer CD147, is vital for tumor cell invasion and blood supply regulation.
- Uveal melanoma is a significant intraocular malignancy where understanding invasion and metastasis is critical.
Purpose of the Study:
- To investigate the correlation between CD147 and MMP-2 expression in uveal melanoma.
- To assess the relationship of CD147 and MMP-2 expression with prognostic factors and vascularization in uveal melanoma.
Main Methods:
- Analyzed CD147 and MMP-2 expression in 49 uveal melanoma samples using immunofluorescence.
- Correlated expression levels with prognostic factors, vasculogenic mimicry, mature vasculature, and tumor-induced angiogenesis.
- Utilized triple immunofluorescence staining with markers for glial cells (GFAP), endothelial cells (CD34), and macrophages (CD68) to determine CD147 and MMP-2 localization.
Main Results:
- CD147 and MMP-2 were expressed in 96% of uveal melanomas, with CD147 up-regulation significantly correlating with higher MMP-2 expression.
- No significant difference in CD147/MMP-2 expression was found between metastatic and non-metastatic groups.
- In non-metastatic cases, clustered CD147-positive cells correlated with tumor size (basal diameter, height) and TNM stage.
Conclusions:
- CD147 may regulate MMP-2 expression in uveal melanoma cells.
- While CD147 and MMP-2 are prevalent, their expression levels do not directly correlate with overall metastatic disease in this cohort.
- Specific patterns of CD147 expression in non-metastatic tumors are associated with established prognostic indicators.
