Melanomas containing more elastin are associated with higher stages of the disease. The interaction between elastin-derived peptides and melanoma cells appears to play an important role in the progression of melanomas. The effects of the elastin-derived peptides VGVAPG and VAPG have been investigated on the migration, invasion, adhesion and angiogenesis of human melanoma cells of different invasive potential. Elastin, tropoelastin and VGVAPG peptide were demonstrated at the invasion site of melanoma using histochemistry and immunohistochemistry. Not only the VGVAPG elastin-derived peptide, which exhibits the XGXXPG consensus sequence in its primary structure, but also the shorter VAPG bind directly to 3 cell surface receptors: galectin-3, integrin avb3 and elastin-binding protein. Our results suggest that the increased levels of elastin-derived peptides facilitate the invasion of melanoma cells: (i) VGVAPG and VAPG elastin-derived peptides are chemotactic for melanoma cells; (ii) they can increase the migration of melanoma cells and the expression of CXCR-4 and CXCL-12 chemokines; (iii) they enhance the expression of the elastin-degrading MMP-2 and MMP-3; (iv) they increase the attachment of melanoma cells and the expression of different adhesion molecules; (v) they increase the expression of the lymphangiogenic VEGF-C and (vi) the galectin-3 receptor can mediate all these effects. Clinical and therapeutic aspects are also discussed. ' 2007 Wiley-Liss, Inc.Key words: melanoma; invasion; elastin; galectin-3 Recently, the incidence of melanomas has significantly increased, and patients have a reduced life expectancy. 1 Malignant melanomas are characterized as tumors of aggressive biological behavior with high motility and metastatic potential. 2,3 The extracellular matrix (ECM) plays a key role in the growth and invasion of tumor cells. Melanoma cells specifically interact with unique matrix proteins such as elastin, especially in elastin-rich organs such as the skin, lung and blood vessels. 4,5 Melanomas containing more elastin are associated with higher stages of the disease: lymph node or distant metastases, higher Clark-level and greater tumor thickness. 6 Several enzymes belonging to the matrix metalloproteinases (MMPs), serine and cysteine proteases superfamily mediate the degradation of elastin. [7][8][9] The level of these enzymes is increased in various stages of the disease 10,11 and leads to the generation of elastin-derived peptides (EDPs), which alter tissue homeostasis. EDPs have several biological effects on a wide range of cells including normal and tumor cells, 12 for example cell proliferation, 13,14 migration and chemotaxis, 15,16 tumor progression, 5,17-20 endothelial cell migration and angiogenesis. 21 These effects of EDPs are mediated predominantly by 3 cellsurface receptors: elastin binding protein (EBP), integrin avb3 and galectin-3 receptors. EBP is a 67-kDa multifunctional receptor containing lectin-binding site [22][23][24][25] and further identified as an enzymatically inactive form of...

No abstract

No abstract

High tissue TGF-beta1 quantity in healthy nasal mucosa without its active form on the cell surface and its low quantity in polyps may reflect its essential role in the inhibitory mechanisms of nasal polyposis. Interleukin-5 plays a key role in the eosinophil recruitment and activation, and both atopic and nonatopic pathways might activate this process. The main sources of IL-5 and TGF-beta1 are the eosinophils and macrophages. Immediate hypersensitivity, besides other mechanisms, might be related to atopic polyps, but the involvement of other, local allergic mechanisms in IgE production of nonatopic polyp tissue cannot be excluded.

Histidine decarboxylase (HDC) is expressed by the cells of melanoma, in which the histamine content tends to be relatively high. This study shows that elevated expression of HDC was found by western blot analysis of primary and metastatic melanoma tissue using a polyclonal HDC specific antibody. The specificity of anti-HDC antibody was confirmed by inhibition of HDC translation (i.e., immunopositivity) in melanoma cells by HDC-specific antisense oligonucleotide. Moreover, the decrease in proliferation caused by HDC antisense oligonucleotides indicates considerable functional relevance of histamine synthesis in melanoma growth and suggests a possible in situ application of specific antisense oligonucleotides for HDC in melanoma therapy.