Basic fibroblast growth factor production and growth factor receptors as potential targets for melanoma therapy.
A number of growth factors can stimulate the proliferation of human malignant melanoma cell lines. We investigated the effects of exogenous growth factors including basic fibroblast growth factor (bFGF), epidermal growth factor, transforming growth factor-alpha, insulin, insulin-like growth factor-I (IGF-I), acidic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta and nerve growth factor on six human metastatic melanoma cell lines. The mitogenic activity of each growth factor was tested using the [3H]thymidine incorporation assay. There was a variable response of the different cell lines to most growth factors. All of the melanoma cell lines tested responded to IGF-I. Furthermore, the effects of growth factors were additive, a combination of bFGF and IGF-I having the greatest effect on three melanoma cell lines tested. The quantitative radioimmunoassay for bFGF and [125I]bFGF binding assay revealed that all of these melanoma cell lines produced bFGF and expressed high affinity receptors for bFGF. A 20-mer antisense oligodeoxynucleotide against the AUG initiation site of the bFGF coding region inhibited the proliferation of Mel-Tang by 40% (p less than 0.0001) and that of SK-MEL-5 by 20% (p less than 0.005), suggesting that these cell lines are at least under partial autocrine control of proliferation by bFGF. The presence of bFGF receptors on a high percentage of melanoma cell lines makes these a potential target for melanoma therapy.
Kato
J
J
Department of Medicine, Roger Williams Medical Center, Providence, RI.
Wanebo
H
H
Calabresi
P
P
Clark
J W
JW
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D016373:DNA, Antisense / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000187:drug effects; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016373:DNA, Antisense; D006133:Growth Substances; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I