Basic fibroblast growth factor and ultraviolet B transform melanocytes in human skin

Carola Berking, Richelle Takemoto, Kapaettu Satyamoorthy, Rosalie Elenitsas, Meenhard Herlyn

    Research output: Contribution to journalArticle

    63 Citations (Scopus)

    Abstract

    Ultraviolet (UV) light is an epidemiological risk factor for melanoma, but its specific contribution to melanoma induction is not known. The first critical step of melanoma development, ie, the uncontrolled proliferation of melanocytes, may be induced by a combination of UV damage and an imbalance of growth factor production by cells in the immediate area of the melanocyte. Among several candidates, basic fibroblast growth factor (bFGF) is the major autocrine growth factor in melanoma and associated with tumor progression. Overexpression of bFGF via adenoviral gene transfer in human skin xenografted to severe combined immunodeficiency mice led to black-pigmented macules within 3 weeks of treatment. Immunofluorescence analysis demonstrated pathological hyperpigmentation, proliferation and hyperplasia of activated melanocytes, but no malignant transformation. Similar changes were observed in skin reconstructs. When bFGF was combined with UVB, pigmented lesions with hyperplastic melanocytic cells were detected, including a lesion with high-grade atypia resembling lentiginous forms of malignant melanoma. Donor-matched control grafts revealed no melanocytic changes, bFGF was overexpressed in dermal fibroblasts demonstrating the cocarcinogenic influence of paracrine-acting growth factors by cells of the microenvironment. This is the first report suggesting that an imbalance of physiological growth factor production in the skin may cause melanoma in combination with UVB.

    Original languageEnglish
    Pages (from-to)943-953
    Number of pages11
    JournalAmerican Journal of Pathology
    Volume158
    Issue number3
    DOIs
    Publication statusPublished - 2001

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    Melanocytes
    Fibroblast Growth Factor 2
    Melanoma
    Skin
    Intercellular Signaling Peptides and Proteins
    Cellular Microenvironment
    Severe Combined Immunodeficiency
    Hyperpigmentation
    Ultraviolet Rays
    Hyperplasia
    Fluorescent Antibody Technique
    Fibroblasts
    Transplants
    Genes
    Neoplasms

    All Science Journal Classification (ASJC) codes

    • Pathology and Forensic Medicine

    Cite this

    Berking, Carola ; Takemoto, Richelle ; Satyamoorthy, Kapaettu ; Elenitsas, Rosalie ; Herlyn, Meenhard. / Basic fibroblast growth factor and ultraviolet B transform melanocytes in human skin. In: American Journal of Pathology. 2001 ; Vol. 158, No. 3. pp. 943-953.
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    abstract = "Ultraviolet (UV) light is an epidemiological risk factor for melanoma, but its specific contribution to melanoma induction is not known. The first critical step of melanoma development, ie, the uncontrolled proliferation of melanocytes, may be induced by a combination of UV damage and an imbalance of growth factor production by cells in the immediate area of the melanocyte. Among several candidates, basic fibroblast growth factor (bFGF) is the major autocrine growth factor in melanoma and associated with tumor progression. Overexpression of bFGF via adenoviral gene transfer in human skin xenografted to severe combined immunodeficiency mice led to black-pigmented macules within 3 weeks of treatment. Immunofluorescence analysis demonstrated pathological hyperpigmentation, proliferation and hyperplasia of activated melanocytes, but no malignant transformation. Similar changes were observed in skin reconstructs. When bFGF was combined with UVB, pigmented lesions with hyperplastic melanocytic cells were detected, including a lesion with high-grade atypia resembling lentiginous forms of malignant melanoma. Donor-matched control grafts revealed no melanocytic changes, bFGF was overexpressed in dermal fibroblasts demonstrating the cocarcinogenic influence of paracrine-acting growth factors by cells of the microenvironment. This is the first report suggesting that an imbalance of physiological growth factor production in the skin may cause melanoma in combination with UVB.",
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    Basic fibroblast growth factor and ultraviolet B transform melanocytes in human skin. / Berking, Carola; Takemoto, Richelle; Satyamoorthy, Kapaettu; Elenitsas, Rosalie; Herlyn, Meenhard.

    In: American Journal of Pathology, Vol. 158, No. 3, 2001, p. 943-953.

    Research output: Contribution to journalArticle

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