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Published on: March 8, 2022
Molecular profiling of ADAM12 and ADAM17 genes in human malignant melanoma
1Department of Surgical Oncology, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania.
Abstract:
ADAM12 and ADAM17 proteins belong to a family of transmembrane disintegrin-containing metalloproteinases (ADAMs) involved in the proteins ectodomain shedding and cell-cell and cell-matrix interactions. However, the specific biological functions of ADAMs are still unclear and, until now, these proteins were not investigated yet in melanoma. The aim of this study was to analyze the splicing variants of ADAM12 (L and S) and ADAM17 gene expression in melanoma at transcriptional and translational level in comparison with control (non-tumor) tissues. Taking in account that ADAM17 sheddase is involved in the modulation of TNF-α (tumor necrosis factor alpha), we analyzed also this cytokine in the plasma of the same patients before any treatment, and we compared the results with healthy controls. Quantitative-RT-PCR and immunohistochemistry were used to analyze ADAM12 and ADAM17 genes expression and the analysis of TNF-α expression was carried out in the plasma using ELISA. We demonstrated that ADAM12L splicing variant together with ADAM17 gene are strongly overexpressed in melanomas, whereas ADAM12S, although up-regulated when compared with the non-tumor controls, the difference was not statistically significant. When we compared the levels of expression for the ADAMs genes according to the tumor stage, we observed that all three investigated genes were significantly overexpressed in advanced stage in comparison with early stage melanomas. In the plasma of the same patients, the expression of TNF-α was up-regulated and significantly correlated with the expression of ADAM17 and respectively, with the advanced tumor stage.
Insights
Melanoma tissues show overexpression of ADAM12L and ADAM17, with higher levels in advanced stages. Tumor necrosis factor alpha (TNF-α) plasma levels also increase with tumor progression, correlating with ADAM17 expression.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- ADAM12 and ADAM17 are metalloproteinases involved in ectodomain shedding and cell interactions.
- Their specific roles in melanoma remain largely uncharacterized.
- This study investigates ADAM12 and ADAM17 expression in melanoma for the first time.
Purpose of the Study:
- To analyze ADAM12 (L and S variants) and ADAM17 gene expression in melanoma.
- To compare gene expression at transcriptional and translational levels with non-tumor tissues.
- To investigate the correlation between ADAM17, tumor necrosis factor alpha (TNF-α), and melanoma progression.
Main Methods:
- Quantitative-RT-PCR and immunohistochemistry were used to assess ADAM12 and ADAM17 gene expression.
- ELISA was employed to measure TNF-α levels in patient plasma.
- Expression levels were analyzed in relation to melanoma stage.
Main Results:
- ADAM12L splicing variant and ADAM17 were significantly overexpressed in melanoma tissues compared to controls.
- ADAM12S showed upregulation but not statistical significance.
- All three genes (ADAM12L, ADAM12S, ADAM17) were significantly overexpressed in advanced-stage melanomas.
- Plasma TNF-α levels were elevated in patients and correlated with ADAM17 expression and advanced tumor stage.
Conclusions:
- ADAM12L and ADAM17 are upregulated in melanoma, particularly in advanced stages.
- Increased TNF-α in plasma is associated with melanoma progression and ADAM17 expression.
- These findings suggest ADAM12 and ADAM17 as potential biomarkers for melanoma.
