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Updated: Jun 16, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
RAGE and S100 protein transcription levels are highly variable in human melanoma tumors and cells
Estelle Leclerc1, Claus W Heizmann, Stefan W Vetter
1Department of Pharmaceutical Sciences, NDSU, Fargo, ND 58108-6950, USA. Estelle.Leclerc@ndsu.edu
Abstract:
The Receptor for Advanced Glycation Endproducts (RAGE) has been suggested to play an important role in melanoma. Animal studies with anti-RAGE antibodies have shown that RAGE blockade leads to reduced melanoma tumor growth and metastasis formation. RAGE is a multiligand receptor and among its ligands are the Ca-binding S100 proteins. Certain S100 proteins are differentially expressed in melanoma. For example, S100B is currently used as a reliable prognostic biomarker in patients with malignant melanoma. We have surveyed 40 human melanoma tumor samples for the transcription of RAGE and five of its known S100 protein ligands. Compared to normal skin tissue, we found highly significant (p < 0.0001) over-expression of S100B and underexpression of S100A2, whereas no significant difference in transcription of S100A6 and S100A10 was observed. RAGE showed slightly increased transcription in stage IV. Between individual tumor samples tremendous differences in transcription of the S100 proteins were observed, whereas RAGE expression showed relatively little variance. We also analyzed three well-characterized melanoma cell lines for S100 and RAGE expression. The S100 protein transcription profile showed clear differences between cultured melanoma cells and melanoma tumor tissue. Detailed profiling of S100 and RAGE transcription in melanoma tumors in combination with imunohisto-chemical and clinical data may lead to improved molecular diagnostic of melanoma and subsequently may facilitate improved treatment in the future.
Insights
The Receptor for Advanced Glycation Endproducts (RAGE) and its S100 ligands show altered expression in melanoma. Profiling these markers may improve melanoma diagnostics and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- The Receptor for Advanced Glycation Endproducts (RAGE) is implicated in melanoma progression.
- RAGE ligands, including S100 proteins, are differentially expressed in melanoma.
- S100B is an established prognostic biomarker for malignant melanoma.
Purpose of the Study:
- To investigate the transcription of RAGE and its S100 ligands in human melanoma tumors.
- To compare gene expression profiles between melanoma tumors and cell lines.
- To explore the potential of RAGE and S100 protein expression for melanoma diagnostics.
Main Methods:
- Analysis of RAGE and five S100 protein ligand transcriptions in 40 human melanoma tumor samples.
- Comparison of gene expression between tumor tissue and normal skin.
- Assessment of RAGE and S100 expression in three melanoma cell lines.
Main Results:
- Significant overexpression of S100B and underexpression of S100A2 in melanoma compared to normal skin (p < 0.0001).
- No significant difference in S100A6 and S100A10 transcription.
- Slightly increased RAGE transcription in stage IV melanoma; significant inter-tumor variability in S100 expression, but low variance in RAGE.
- Melanoma cell lines showed distinct S100 transcription profiles compared to tumor tissue.
Conclusions:
- RAGE and specific S100 proteins exhibit differential expression patterns in melanoma.
- S100 protein expression varies significantly between melanoma tumors and cell lines.
- Combined analysis of RAGE/S100 transcription with clinical data could enhance melanoma molecular diagnostics and treatment strategies.
