MCAM, as a novel receptor for S100A8/A9, mediates progression of malignant melanoma through prominent activation of NF-κB and ROS formation upon ligand binding

Abstract

The dynamic interaction between tumor cells and their microenvironment induces a proinflammatory milieu that drives cancer development and progression. The S100A8/A9 complex has been implicated in chronic inflammation, tumor development, and progression. The cancer microenvironment contributes to the up-regulation of this protein complex in many invasive tumors, which is associated with the formation of pre-metastatic niches and poor prognosis. Changing adhesive preference of cancer cells is at the core of the metastatic process that governs the reciprocal interactions of cancer cells with the extracellular matrices and neighboring stromal cells. Cell adhesion molecules (CAMs) have been confirmed to have high-level expression in various highly invasive tumors. The expression and function of CAMs are profoundly influenced by the extracellular milieu. S100A8/A9 mediates its effects by binding to cell surface receptors, such as heparan sulfate, TLR4 and RAGE on immune and tumor cells. RAGE has recently been identified as an adhesion molecule and has considerably high identity and similarity to ALCAM and MCAM, which are frequently over-expressed on metastatic malignant melanoma cells. In this study, we demonstrated that ALCAM and MCAM also function as S100A8/A9 receptors as does RAGE and induce malignant melanoma progression by NF-κB activation and ROS formation. Notably, MCAM not only activated NF-κB more prominently than ALCAM and RAGE did but also mediated intracellular signaling for the formation of lung metastasis. MCAM is known to be involved in malignant melanoma development and progression through several mechanisms. Therefore, MCAM is a potential effective target in malignant melanoma treatment.

Neuroplastin‐β mediates S100A8/A9‐induced lung cancer disseminative progression

“…Quantitative real-time PCR was performed as described previously. 10 Table S1. siRNAs and decoy DNAs were transfected using Lipofectamin RNAiMAX reagent (Thermo Fisher Scientific).…”

Multi-omics Analysis of Serum Samples Demonstrates Reprogramming of Organ Functions Via Systemic Calcium Mobilization and Platelet Activation in Metastatic Melanoma

“…Peptides had to be identified only once over the whole chromatographic run (multiple identifications were only accepted for very broad peaks) and had to be identified in at least two of the three different sample types (low TL, high TL, control). Thereby, 940 transitions for 188 peptides (93 proteins) were used for unscheduled MRM measurements, applying different dwell times depending on the intensities achieved for peptide precursors in shotgun MS: 100ms for those with the lowest intensities (Ͻ10 6 ), 50ms for those with moderate intensities (10 6 -10 7 ), and 20ms for those with highest signal intensities (Ͼ10 7 ). One biological sample, each of the low TL, high TL and control group, previously used for shotgun MS, was injected multiple times for measuring the 940 selected transitions in unscheduled MRM mode.…”

“…Actually, in melanoma, PMEL is most widely used as melanoma marker in serum samples (6). Chondroitin sulfate proteoglycan 4 and S100A8 and S100A9 have been reported to be upregulated during melanoma progression (7).…”

Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells

“…CD146/ MCAM was previously considered as an endothelial cell marker and has been used for the identification of circulating endothelial cells (24). It is now known to be also expressed by melanoma cells (17) and is associated with melanoma metastasis (25)(26)(27). There are two CD146/MCAM isoforms, CD146-long and CD146-short.…”