Melanocortin 1 Receptor Regulates Melanoma Cell Migration by Controlling Syndecan-2 Expression

Chung, Heesung; Lee, Jung-Hyun; Jeong, Dayun; Han, Inn Oc; Oh, Eok Soo

doi:10.1074/jbc.m111.334730

Cited by 36 publications

(29 citation statements)

References 33 publications

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“…Interestingly, human Tregs expanded via α-MSH-stimulated DCs suppressed the proliferation and cytokine secretion of T-helper-17 (Th17) cells [91]. As α-melanocyte-stimulating hormone is a ligand for the melanocortin 1 receptor (MC1R), which expressed on and play a role in malignant cell function through the Wnt/β-catenin pathway [92], its role in formation and action of tumorassociated regDCs should be further investigated.…”

Section: Additional Tolerogenic Pathways In Regdcs: Neuropeptidesmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Shurin

2013

Cancer Microenvironment

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Three major functional subsets of dendritic cells (DCs) have been described in the tumor microenvironment in patients with cancer and tumor-bearing animals: (i) conventional DCs with intact antigen-presenting capabilities, (ii) functionally defective DCs with decreased motility and low ability to uptake, process and present antigens or produce cytokines and (iii) regulatory DCs with high capacity to suppress T cell proliferation, induce differentiation of regulatory T cells or support immune tolerance. Phenotypic characteristics of regulatory DCs (regDCs), as well as the mechanisms of T cell inhibition, vary in different experimental conditions and environments, suggesting high level of their plasticity and probably different origin. Although new data demonstrate that regDCs may play an important role at early stages of tumor development, functional differences and clinical significance of emergence of different myeloid regulatory cells (MDSCs, regDCs, M2 macrophages, N2 neutrophils, mast cells) in cancer remain to be determined.

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Section: Additional Tolerogenic Pathways In Regdcs: Neuropeptidesmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Shurin

2013

Cancer Microenvironment

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“…There are also mosaic vessels in solid tumors where both endothelial cells and cancer cells form the luminal surface [38]. Recently, it was shown that MC1R overexpression in melanoma cells enhanced the synthesis of syndecan-2, a cell surface heparan sulfate proteoglycan [39]. Therefore, the presence of negatively charged areas due to syndecan-2 overexpression in mosaic vessels of melanoma tumor may also enhance polyplex binding.…”

Section: Resultsmentioning

confidence: 99%

“…(2010) [46], the effect of “binding site barrier” was observed only with 25 nm-sized nanoparticles but not with 60 nm ones indicating dependence of tissue penetration on particles’ size. The next factor responsible for impeded diffusion of macromolecules (including polyplexes) is negatively charged basement membrane of endothelium [36], extracellular matrix [51] or melanoma cancer cells surface [39]. The point is that many of the solid tumors have increased content of glycosaminoglycans and especially hyaluronan [52, 53].…”

Section: Resultsmentioning

confidence: 99%

Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue

et al. 2013

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Targeted sodium-iodide symporter (NIS) gene transfer can be considered as a promising approach for diagnostics of specific types of cancer. For this purpose we used targeted polyplexes based on PEI–PEG–MC1SP block-copolymer containing MC1SP-peptide, a ligand specific for melanocortin receptor-1 (MC1R) overexpressed on melanoma cells. Targeted polyplexes demonstrated enhanced NIS gene transfer compared to non-targeted (lacking MC1SP) ones in vitro. Using dorsal skinfold chamber and intravital microscopy we evaluated accumulation and microdistribution of quantum dot-labeled polyplexes in tumor and normal subcutaneous tissues up to 4 hours after intravenous injection. Polyplexes demonstrated significantly higher total accumulation in tumor tissue in comparison with subcutaneous ones (control). Targeted and non-targeted polyplexes extravasated and penetrated into the tumor tissue up to 20 μm from the vessel walls. In contrast, in normal subcutaneous tissue polyplexes penetrated less than 5 μm from the vessel walls with the level of extravasated polyplexes 400-fold less than in tumor. Accumulated polyplexes in tumor tissue caused NIS gene expression. Subsequent 123I- intravenous injection resulted in 6.8 ± 1.1 and 4.5 ± 0.8 % ID/g (p < 0.001) iodide accumulation in tumors in the case of targeted and non-targeted polyplexes, respectively, as was shown using SPECT/CT.

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“…MC1R expression level is connected with melanoma cell migration: the higher the level, the higher the migration ability of cells is [67]. MC1R decreases the activity of stress response by p38 MAPK kinase, increasing the expression of syndecane-2, which is involved in increasing melanoma cell motility.…”

Section: Role Of Mc1r In Melanoma Formation Development and Preventionmentioning

confidence: 99%

“…MC1R can affect the microphthalmia-associated transcription factor via protein kinase A (PKA), as well as via oncogenic signaling pathway RAS/RAF/MEK/ERK by Src-dependent c-KIT activation [69]. Additionally, MC1R promotes melanoma cell migration due to enhancement of syndecane-2 (Sdc2) expression [67]. …”

Section: Figmentioning

confidence: 99%

Malignant melanoma and melanocortin 1 receptor

Rosenkranz

Slastnikova

Durymanov

et al. 2013

Biochemistry Moscow

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The conventional chemotherapeutic treatment of malignant melanoma still remains poorly efficient in most cases. Thus the use of specific features of these tumors for development of new therapeutic modalities is highly needed. Melanocortin receptor-1 (MC1R) overexpression on the cell surface of the vast majority of human melanomas, making MC1R a valuable marker of these tumors, is one of these features. Naturally, MC1R plays a key role in skin protection against damaging ultraviolet radiation by regulating eumelanin production. MC1R activation is involved in regulation of melanocyte cell division. This article reviews the peculiarities of regulation and expression of MC1R, melanocytes, and melanoma cells, along with the possible connection of MC1R with signaling pathways regulating proliferation of tumor cells. MC1R is a cell surface endocytic receptor, thus considered perspective for diagnostics and targeted drug delivery. A number of new therapeutic approaches that utilize MC1R, including endoradiotherapy with Auger electron and α- and β-particle emitters, photodynamic therapy, and gene therapy are now being developed.

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Melanocortin 1 Receptor Regulates Melanoma Cell Migration by Controlling Syndecan-2 Expression

Cited by 36 publications

References 33 publications

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Microdistribution of MC1R-targeted polyplexes in murine melanoma tumor tissue

Malignant melanoma and melanocortin 1 receptor

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