Regulation of human melanoma growth and metastasis by AGE-AGE receptor interactions
Regulation of human melanoma growth and metastasis by AGE-AGE receptor interactions
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DOI：
10.1046/j.0022-202x.2004.22218.x
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发表时间：
2004-02-01
影响因子：
6.5
通讯作者：
Shimizu, H
中科院分区：
文献类型：
--
作者：
Abe, R;Shimizu, T;Shimizu, H
晚期糖基化终末产物（AGE）是一种非酶糖化蛋白衍生物，与糖尿病血管病变（包括皮肤病变）的发生和发展有关。然而，AGE参与黑色素瘤的发展和进展尚未完全阐明。在这项研究中，我们调查了他们的受体AGE（AGE）在人黑色素瘤的表达水平，并随后研究了AGE对黑色素瘤生长和迁移的影响。首先，在人黑色素瘤细胞（G361和A375）的细胞质中检测到H2 O2。在不同类型的AGE中，甘油醛和乙醇酸衍生的AGE显著刺激人黑色素瘤细胞的生长和迁移。此外，通过用抗人黑色素瘤中和抗体治疗，可预防无胸腺小鼠中黑素瘤细胞异种移植物的肿瘤形成。在荷瘤小鼠中，通过使用抗-β-CD中和抗体治疗，存活率延长，自发性肺转移被抑制。此外，所有AGE都存在于人类黑色素瘤瘤床中，而在正常皮肤中几乎检测不到。这些结果表明，AGE可能参与黑色素瘤的生长和侵袭，通过相互作用，并代表有前途的候选人，评估未来的治疗潜力，这种疗法治疗黑色素瘤患者。
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.