Fully human antibodies to MCAM/MUC18 inhibit tumor growth and metastasis of human melanoma.

ABX试验 黑色素瘤 转移 癌症研究 基质凝胶 血管生成 血管生成拟态 体内 体外 化学 生物 癌症 医学 内科学 数学 生物技术 统计 生物化学
作者
Lisa D. Mills,Carmen S. Tellez,Suyun Huang,Cheryl H. Baker,Marya F. McCarty,Larry Green,Jean M. Gudas,Xiaoshan Feng,Menashe Bar-Eli
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期刊:PubMed 卷期号:62 (17): 5106-14 被引量:58
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MCAM/MUC18 expression correlates with tumor thickness and metastatic potential of human melanoma cells in nude mice. Moreover, ectopic expression of MUC18 in primary cutaneous melanoma cells leads to increased tumor growth and metastasis in vivo. Here we tested the effect of a fully human anti-MUC18 antibody, ABX-MA1, on angiogenesis, tumor growth, and metastasis. ABX-MA1 had no effect on melanoma cell proliferation rate in vitro. However, when cells of the metastatic melanoma lines A375SM and WM2664 (which express high levels of MUC18) were injected s.c. into nude mice and treated with ABX-MA1 (100 micro g, weekly, i.p. for 5 weeks), tumor growth was significantly inhibited compared with control IgG-treated mice. ABX-MA1 treatment also suppressed experimental lung metastasis of these melanoma cells. ABX-MA1 disrupted spheroid formation by melanoma cells expressing MUC18 (homotypic interaction) and the ability of these cells to attach to human vascular endothelial cells [HUVECs (MUC18 positive)] in vitro. ABX-MA1 treatment of melanoma cells in vitro significantly inhibited the promoter and collagenase activity of matrix metalloproteinase 2, resulting in decreased invasion through Matrigel-coated filters. Decreased expression of matrix metalloproteinase 2 was also observed in the implanted tumors in vivo. Moreover, because HUVECs also express MUC18, ABX-MA1 directly disrupted the tube-like formation by HUVECs in an in vitro vessel formation assay. Collectively, these results point to usefulness of ABX-MA1 as a modality to treat melanoma either alone or in combination with conventional chemotherapy or other antitumor agents.

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