Transforming growth factor-β1 increases survival of human melanoma through stroma remodeling

Carola Berking, Richelle Takemoto, Helmut Schaider, Louise Showe, Kapaettu Satyamoorthy, Paul Robbins, Meenhard Herlyn

    Research output: Contribution to journalArticle

    131 Citations (Scopus)

    Abstract

    Transforming growth factor (TGF)-β is growth inhibitory for normal epithelial cells and melanocytes but can stimulate mesenchymal cells. Resistance to its inhibitory effects is characteristic of human melanoma, the growth of which may instead be promoted by TGF-β, because its production is increased with melanoma progression. Whether TGF-β has an autocrine function for melanoma cells or is important for paracrine stimulation of the tumor stroma is not known. In this study, TGF-β1 was expressed in melanoma cells via adenoviral gene transfer, and tumor growth was analyzed in vitro, in human skin grafts, and in mixtures with fibroblasts that were injected s.c. into immunodeficient mice. The TGF-β1 produced by the melanoma cells activated the fibroblasts to produce matrix within and around the tumor mass, whereas control tumors showed less stroma and more cell death. High expression of collagen, fibronectin, tenascin, and α2 integrin was detected in the TGF-β1-expressing tumors by immunohistochemistry. Number and size of lung metastases were significantly increased. cDNA expression array analysis of TGF-β1-transduced fibroblasts embedded in type I collagen and of TGF-β1-transduced melanoma cells demonstrated induction of types XV, XVIII, and VI collagens, tenascin, plasminogen activator inhibitor-I, vascular endothelial growth factor, cysteine-rich fibroblast growth factor receptor-1, and platelet-derived growth factor receptor-β, which could be linked to promotion of growth and survival in melanoma. These data suggest that remodeling of the neighboring stroma, which provides a supporting scaffolding and a positive feedback stimulation of tumor growth, is an important function of TGF-β1 in melanoma.

    Original languageEnglish
    Pages (from-to)8306-8316
    Number of pages11
    JournalCancer Research
    Volume61
    Issue number22
    Publication statusPublished - 15-11-2001

    Fingerprint

    Transforming Growth Factors
    Melanoma
    Survival
    Tenascin
    Growth
    Neoplasms
    Fibroblasts
    Collagen Type XVIII
    Collagen Type VI
    Receptor, Fibroblast Growth Factor, Type 1
    Platelet-Derived Growth Factor Receptors
    Plasminogen Inactivators
    Melanocytes
    Collagen Type I
    Oligonucleotide Array Sequence Analysis
    Fibronectins
    Integrins
    Vascular Endothelial Growth Factor A
    Cell Death
    Collagen

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

    Cite this

    Berking, C., Takemoto, R., Schaider, H., Showe, L., Satyamoorthy, K., Robbins, P., & Herlyn, M. (2001). Transforming growth factor-β1 increases survival of human melanoma through stroma remodeling. Cancer Research, 61(22), 8306-8316.
    Berking, Carola ; Takemoto, Richelle ; Schaider, Helmut ; Showe, Louise ; Satyamoorthy, Kapaettu ; Robbins, Paul ; Herlyn, Meenhard. / Transforming growth factor-β1 increases survival of human melanoma through stroma remodeling. In: Cancer Research. 2001 ; Vol. 61, No. 22. pp. 8306-8316.
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    Berking, C, Takemoto, R, Schaider, H, Showe, L, Satyamoorthy, K, Robbins, P & Herlyn, M 2001, 'Transforming growth factor-β1 increases survival of human melanoma through stroma remodeling', Cancer Research, vol. 61, no. 22, pp. 8306-8316.

    Transforming growth factor-β1 increases survival of human melanoma through stroma remodeling. / Berking, Carola; Takemoto, Richelle; Schaider, Helmut; Showe, Louise; Satyamoorthy, Kapaettu; Robbins, Paul; Herlyn, Meenhard.

    In: Cancer Research, Vol. 61, No. 22, 15.11.2001, p. 8306-8316.

    Research output: Contribution to journalArticle

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    AU - Berking, Carola

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    AU - Herlyn, Meenhard

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    Berking C, Takemoto R, Schaider H, Showe L, Satyamoorthy K, Robbins P et al. Transforming growth factor-β1 increases survival of human melanoma through stroma remodeling. Cancer Research. 2001 Nov 15;61(22):8306-8316.