No abstract

Advanced glycation end products (AGE), nonenzymatically glycated protein derivatives, have been implicated in the development and progression of diabetic angiopathies, including skin dermopathy. Nevertheless, the involvement of AGE in the development and progression of melanoma has not been fully elucidated. In this study we investigated the expression levels of their receptor for AGE (RAGE) in human melanoma and subsequently studied the effects of AGE on melanoma growth and migration. First, RAGE was detected in the cytoplasm of human melanoma cells (G361 and A375). Among the different types of AGE, glyceraldehyde- and glycolaldehyde-derived AGE significantly stimulated the growth and migration of human melanoma cells. Furthermore, tumor formation of melanoma cell xenografts in athymic mice was prevented by treatment with anti-RAGE neutralizing antibodies. In tumor-bearing mice, survival rates were prolonged, and spontaneous pulmonary metastases were inhibited by treatment using anti-RAGE neutralizing antibodies. In addition, all AGE were present in beds of human melanoma tumor, whereas they were barely detected in normal skin. These results suggest that AGE might be involved in the growth and invasion of melanoma through interactions with RAGE and represent promising candidates for assessing the future therapeutic potential of this therapy in treating patients with melanoma.

No abstract

Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, and is involved in the pathogenesis of angiogenic eye disease such as proliferative diabetic retinopathy. However, a functional role for PEDF in tumor growth and angiogenesis remains to be determined. In this study, we have investigated both the in vitro and in vivo growth characteristics of human malignant melanoma G361 cell lines, stably transfected to overexpress human PEDF. Expression levels of PEDF proteins in melanoma cell lines G361 and A375 were comparable with that of human cultured melanocytes, whereas vascular endothelial growth factor levels in two tumor cell lines were much stronger than that in normal melanocytes. Overexpression of PEDF was found to significantly inhibit tumor growth and vessel formation in G361 nude mice xenografts. Furthermore, in vitro proliferation rates of G361 cells were decreased in PEDFtransfected cells. PEDF proteins showed dose-dependent induced growth retardation and apoptotic cell death in nontransfected G361 cells, which were completely prevented by treatment with antibodies against the Fas ligand. Our present study highlights two beneficial effects of PEDF treatment on melanoma growth and expansion; one is the suppression of tumor angiogenesis, and the other is induction of Angiogenesis, a process by which new vascular networks are formed from pre-existing capillaries, is required for tumors to grow, invade, and metastasize.

IL-6 expression is inversely related to cell proliferation and positively related to differentiation in cholangiocarcinoma.