Abstract
Unlike normal melanocytes, primary and metastatic human melanomas express high levels of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) messenger RNA, and expression of these genes is essential in sustaining the proliferation of malignant melanomas in vitro. To determine whether bFGF and FGFR-1 are also required for tumor formation in these cells, liposome-mediated gene transfer was used to deliver episomal vectors containing antisense-oriented bFGF or FGFR-1 cDNAs into human melanomas, grown as subcutaneous tumors in nude mice. The growth of tumors injected with these constructs was completely arrested or the tumors regressed as a result of blocked intratumoral angiogenesis and subsequent necrosis. Thus, inhibition of bFGF/FGFR-1-mediated signaling may open a new avenue for the treatment of advanced-stage melanomas.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Division / genetics*
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DNA, Complementary
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factor 2 / metabolism*
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Gene Transfer Techniques
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Humans
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Melanoma / blood supply
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Melanoma / metabolism*
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Melanoma / pathology
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Mice
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Mice, Nude
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Neoplasm Transplantation
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Neovascularization, Pathologic / genetics*
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Oligonucleotides, Antisense / pharmacology*
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Receptor Protein-Tyrosine Kinases*
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Receptor, Fibroblast Growth Factor, Type 1
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Receptors, Fibroblast Growth Factor / genetics
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Receptors, Fibroblast Growth Factor / metabolism*
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Signal Transduction / genetics
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Tumor Cells, Cultured
Substances
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DNA, Complementary
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Oligonucleotides, Antisense
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Receptors, Fibroblast Growth Factor
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Fibroblast Growth Factor 2
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FGFR1 protein, human
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Fgfr1 protein, mouse
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1