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Basic fibroblast growth factor production and growth factor receptors as potential targets for melanoma therapy
J Kato1, H Wanebo, P Calabresi
1Department of Medicine, Roger Williams Medical Center, Providence, RI.
Abstract:
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.
Insights
Human melanoma cells proliferate in response to growth factors. Insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) showed significant effects, suggesting potential therapeutic targets.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Human malignant melanoma cell lines exhibit variable responses to exogenous growth factors.
- Growth factors play a crucial role in stimulating cell proliferation.
Purpose of the Study:
- To investigate the effects of various exogenous growth factors on human metastatic melanoma cell lines.
- To determine the role of basic fibroblast growth factor (bFGF) and its receptors in melanoma cell proliferation.
Main Methods:
- Tested mitogenic activity of nine growth factors using [3H]thymidine incorporation assay.
- Quantified bFGF production and [125I]bFGF binding.
- Utilized antisense oligodeoxynucleotides to inhibit bFGF coding region.
Main Results:
- All tested melanoma cell lines responded to insulin-like growth factor-I (IGF-I).
- Combinations of bFGF and IGF-I demonstrated additive effects, significantly enhancing proliferation in some cell lines.
- Melanoma cell lines produced bFGF and expressed high-affinity bFGF receptors.
- Antisense inhibition of bFGF reduced proliferation, indicating partial autocrine control.
Conclusions:
- Melanoma cell proliferation is influenced by multiple growth factors, with IGF-I and bFGF being particularly significant.
- The expression of bFGF receptors on melanoma cells presents a potential therapeutic target for melanoma treatment.