Upregulation of S100P, receptor for advanced glycation end products and ezrin in malignant melanoma

Abstract

S100P is a member of the S100 family. Increased levels of S100P have been documented in various malignancies. Binding of extracellular S100P to receptor for advanced glycation end products (RAGE) or coupling of intracellular S100P with a cytoskeletal protein, ezrin, play a crucial role in tumor growth, invasion and metastasis. However, little is known about the expression of S100P, RAGE and ezrin in malignant melanoma. We immunostained these three molecules in 20 primary and 20 metastatic melanomas. Samples of 20 benign nevus pigmentosus and 10 of normal skin were tested as controls. The expression levels (percentage of positively stained cells) of S100P, RAGE and ezrin were significantly higher in melanomas than in nevus pigmentosus. Moreover, slightly but significantly higher expression levels were observed in metastatic than in primary melanomas. Significant positive correlations were evident between the expression levels of S100P and RAGE, S100P and ezrin, and RAGE and ezrin, respectively. In conclusion, the coordinate upregulation of S100P, RAGE and ezrin may possibly facilitate malignant transformation of melanoma.

Clinical Implications of High-mobility Group Box-1 (HMGB1) and the Receptor for Advanced Glycation End-products (RAGE) in Cutaneous Malignancy: A Systematic Review

“…Full-text review eliminated six studies due to inappropriate data (use of non-human samples, cell culture only, or animal models) or topic irrelevance to the present review. Ultimately, nine articles were included in this review (25,26,21,(27)(28)(29)(30)(31)(32). The majority of the included studies investigated the role of HMGB1 or RAGE in frozen or formalin-fixed paraffin-embedded (FFPE) tissue from patients with melanoma (25,26,28,29,32).…”

“…In comparison, immunoreactivity of RAGE in nevus pigmentosus was faint in the benign nevus cells (28). Leclerc and colleagues surveyed 40 melanoma tumor samples for RAGE transcription and found elevated levels in stage IV when compared to stage III tumors.…”

Role of miR-647 in human gastric cancer suppression

“…Furthermore, we confirmed that miR-647 overexpression suppressed ANK2 protein expression. Cytoskeletal proteins are positively associated with cell growth and metastasis (19,20). As a member of the cytoskeletal protein family, ANK2 encodes one of the 3 ankyrins: ankyrin-R (ANK1), ankyrin-B (ANK2) and ankyrin-G (ANK3), mediating various integral membrane proteins (21,22).…”

RAGE and its ligands in cancer – culprits, biomarkers, or therapeutic targets?

“…Administration of anti-RAGE antibodies [55], or DNA AGE-aptamer (a short sequence of DNA or RNA with high affinity to cognate ligands [56]) to nude mice with infused melanoma cells significantly inhibited tumor growth, number of tumor-associated vessels and decreased expression levels of proliferating nuclear antigen [57]. Expression of RAGE, S100P and cytoskeletal protein ezrin which all play a role in tumor growth, invasion and metastasis were significantly higher (and closely correlating) in melanoma than in nevus pigmentosus and higher expression levels were observed in metastatic compared to primary melanomas [58]. Pretreatment of melanoma cells with anti-RAGE antibody suppressed migration and invasion and formation of pulmonary metastases of melanoma cells in uteroglobin knockout mice [59].…”