Inhibition of xenografted human melanoma growth and prevention of metastasis development by dual antiangiogenic/antitumor activities of pigment epithelium-derived factor.
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.
Garcia
Marta
M
Project on Damage, Repair and Tissue Engineering CIEMAT and Fundación M. Botin, Madrid, Spain.
Fernandez-Garcia
Nuria Isabel
NI
Rivas
Veronica
V
Carretero
Marta
M
Escamez
Maria J
MJ
Gonzalez-Martin
Alicia
A
Medrano
Estela E
EE
Volpert
Olga
O
Jorcano
Jose L
JL
Jimenez
Benilde
B
Larcher
Fernando
F
Del Rio
Marcela
M
D000818:Animals; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005136:Eye Proteins; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008545:Melanoma / Q000098:blood supply* / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy*; D009414:Nerve Growth Factors; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor