Mutant MCP-1 therapy inhibits tumor angiogenesis and growth of malignant melanoma in mice
Mutant MCP-1 therapy inhibits tumor angiogenesis and growth of malignant melanoma in mice
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DOI：
10.1016/j.bbrc.2007.10.182
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发表时间：
2008-01-11
影响因子：
3.1
通讯作者：
Imaizumi, Tsutomu
中科院分区：
文献类型：
--
作者：
Koga, Mitsuhisa;Kai, Hisashi;Imaizumi, Tsutomu
我们研究了阻断单核细胞趋化因子-1（MCP-1）功能是否会抑制肿瘤相关巨噬细胞（TAM）的募集，并阻止肿瘤血管生成和人类恶性黑色素瘤的肿瘤生长。将B16-F1黑素瘤细胞植入C57 BL/6小鼠的背部（第0天）。在第7天，将显性负性MCP-1突变体（7 ND）基因转染到大腿肌肉中，以使过表达的7 ND蛋白分泌到体循环中。7 ND治疗抑制TAM募集并部分减少肿瘤血管生成和肿瘤生长。此外，7 ND治疗减弱了基质和肿瘤中肿瘤坏死因子-α（TNF α）、白细胞介素-1 α（IL-1 α）和血管内皮生长因子（VEGF）的诱导。黑色素瘤细胞不仅表达MCP-1，而且还表达其受体CCR 2。因此，提示MCP-1将通过TAM募集诱导TNF α、IL-1 α和VEGF以及可能对黑素瘤细胞的直接自分泌/旁分泌作用而在早期阶段增强肿瘤血管生成和早期肿瘤生长。(c)2007爱思唯尔公司All rights reserved.
We investigated whether blocking of monocyte chemoattractant-1 (MCP-1) function would inhibit recruitment of tumor-associated macrophages (TAMs) and prevent tumor angiogenesis and tumor growth of human malignant melanoma. B16-F1 melanoma cells were implanted onto the back of C57BL/6 mice (Day 0). At Day 7, a dominant negative MCP-1 mutant (7ND) gene was transfected in the thigh muscle to make overexpressed 7ND protein secreted into systemic circulation. 7ND treatment inhibited TAM recruitment and partially reduced tumor angiogenesis and tumor growth. Also, 7ND treatment attenuated inductions of tumor necrosis factor-alpha (TNF alpha), interieukin-1 alpha (IL-1 alpha), and vascular endothelial growth factor (VEGF) in the stroma and tumor. Melanoma cells expressed not only MCP-1 but also its receptor CCR2. Accordingly, it was suggested that MCP-1 would enhance tumor angiogenesis and early tumor growth in the early stages by inducing TNF alpha, IL-1 alpha, and VEGF through TAM recruitment and probably the direct autocrine/paracrine effects on melanoma cells. (c) 2007 Elsevier Inc. All rights reserved.