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Growth control of melanoma cells and melanocytes by cytokines
K Krasagakis1, C Garbe, C C Zouboulis
1Department of Dermatology, University Medical Center Steglitz, Free University of Berlin, Germany.
Abstract:
Aberrant proliferation of tumor cells characterizes cancer growth. Investigations of cellular growth control mechanisms have contributed to our understanding of carcinogenesis and to the identification of compounds with specific antitumor activity. Many cytokines have been found to act on melanoma tumors, either produced by the tumor cells themselves or by infiltrating host cells. Purified cytokines allowed direct comparison of the growth response between normal human melanocytes and malignant melanoma cells. The present paper summarizes results of a series of our own experiments not yet published and data from a review of the recent literature. Proliferation of normal human melanocytes is enhanced by several cytokines, including basic fibroblast growth factor (bFGF), melanoma growth stimulatory activity (MGSA), hepatocyte growth factor (HGF), and mast cell growth factor (MGF). Melanoma cells are additionally stimulated by epidermal growth factor (EGF)/transforming growth factor alpha (TGF-alpha) and nerve growth factor (NGF). Tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta 1 (TGF-beta 1), and interleukin (IL)-6 are all potent inhibitors of melanocyte growth, but they are less effective on melanoma cells or even stimulate their growth. Interferon (IFN)-alpha and IFN-gamma inhibited proliferation of melanoma cells but not of melanocytes, whereas IFN-beta showed antiproliferative effects in both cell types. These findings suggest an alteration in growth control mechanisms during melanocyte transformation and possibly play a role in melanoma pathogenesis.
Insights
Cancer cells exhibit uncontrolled proliferation. Cytokines differentially affect normal melanocytes and melanoma cells, revealing altered growth control mechanisms in melanoma pathogenesis.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Cancer is characterized by aberrant tumor cell proliferation.
- Cytokines play a role in melanoma tumor growth, produced by tumor or host cells.
- Understanding cytokine interactions is crucial for cancer research.
Purpose of the Study:
- To compare the effects of various cytokines on normal melanocyte and melanoma cell proliferation.
- To investigate alterations in cellular growth control mechanisms during melanocyte transformation.
- To identify potential therapeutic targets for melanoma.
Main Methods:
- Review of published literature on cytokine effects on melanocytes and melanoma cells.
- Summary of unpublished experimental results.
- Direct comparison of cytokine-induced growth responses in normal human melanocytes and malignant melanoma cells.
Main Results:
- Normal melanocyte proliferation is enhanced by basic fibroblast growth factor (bFGF), melanoma growth stimulatory activity (MGSA), hepatocyte growth factor (HGF), and mast cell growth factor (MGF).
- Melanoma cells show additional stimulation by epidermal growth factor (EGF)/transforming growth factor alpha (TGF-alpha) and nerve growth factor (NGF).
- While tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta 1 (TGF-beta 1), and interleukin (IL)-6 inhibit melanocyte growth, they are less effective or stimulate melanoma cells. Interferon (IFN)-alpha and IFN-gamma inhibit melanoma cell proliferation, but not melanocytes, while IFN-beta has antiproliferative effects on both.
Conclusions:
- Significant alterations in cytokine-mediated growth control occur during melanocyte transformation.
- These altered mechanisms are implicated in melanoma pathogenesis.
- Differential cytokine responses highlight potential therapeutic strategies targeting melanoma growth.