Inhibition of xenografted human melanoma growth and prevention of metastasis development by dual antiangiogenic/antitumor activities of pigment epithelium-derived factor

被引:88
作者
Garcia, M
Fernandez-Garcia, NI
Rivas, V
Carretero, M
Escamez, MJ
Gonzalez-Martin, A
Medrano, EE
Volpert, O
Jorcano, JL
Jimenez, B
Larcher, F
Del Rio, M
机构
[1] UAM, CSIC, Inst Invest Biomed, Dept Biochem, Madrid 28029, Spain
[2] CIEMAT, Project Damage Repair & Tissue Engn, E-28040 Madrid, Spain
[3] Fdn M Botin, Madrid, Spain
[4] Baylor Coll Med, Huffington Ctr Aging, Dept Mol & Cellular Biol & Dermatol, Houston, TX 77030 USA
[5] Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA
关键词
D O I
10.1158/0008-5472.CAN-04-0230
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Human melanoma mortality is associated with the growth of metastasis in selected organs including the lungs, liver, and brain. In this study, we examined the consequences of overexpression of pigment epithelium-derived factor (PEDF), a neurotrophic factor and potent angiogenesis inhibitor, on both melanoma primary tumor growth and metastasis development. PEDF overexpression by melanoma cells greatly inhibited subcutaneous tumor formation and completely prevented lung and liver metastasis in immunocompromised mice after tail vein injection of metastatic human melanoma cell lines. Whereas the effects of PEDF on primary tumor xenografts appear mostly associated with inhibition of the angiogenic tumor response, abrogation of melanoma metastasis appears to depend on direct PEDF effects on both migration and survival of melanoma cells. PEDF-mediated inhibition of melanoma metastases could thus have a major impact on existing therapies for melanoma.
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页码:5632 / 5642
页数:11
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