Co-expression by keratinocytes of migration stimulating factor (MSF) and a functional inhibitor of its bioactivity (MSFI)

Sarah J. Jones, Margaret M. Florence, Ian R. Ellis, Katerina Kankova, Seth L. Schor, Ana M. Schor

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Migration stimulating factor (MSF) is a potent autocrine and paracrine factor expressed by fibroblasts and epithelial cells in foetal skin, tumours and healing wounds. In tissue culture, MSF bioactivity is present in the conditioned medium of foetal and tumour derived fibroblasts, but not in normal adult fibroblasts or keratinocytes. The conditioned medium of early passage keratinocytes or a keratinocyte line (HaCaT) effectively inhibited the motogenic activity of rhMSF. Fractionation of keratinocyte conditioned medium by size-exclusion chromatography revealed the presence of bioactive MSF as well as a functional inhibitor of MSF (MSFI) in fractions corresponding to approximately 70 kDa and 25 kDa, respectively. MSFI was purified and identified as neutrophil gelatinase-associated lipocalin (NGAL or lipocalin-2). Immunostaining confirmed that keratinocytes expressed both MSF and NGAL, whereas normal adult fibroblasts did not express either. Recombinant and cell-produced NGAL neutralised the motogenic activity of rhMSF. NGAL is known to bind MMP-9 and promote the activity of this protease. In contrast, there was no evidence of NGAL-MSF binding in keratinocyte conditioned medium. MSF displays a number of bioactivities of relevance to cancer progression and wound healing. Our findings indicate a novel function of NGAL and a possible mechanism for regulating MSF activity in tissues.
    Original languageEnglish
    Pages (from-to)4145-4157
    Number of pages13
    JournalExperimental Cell Research
    Volume313
    Issue number20
    DOIs
    Publication statusPublished - 2007

    Fingerprint

    Keratinocytes
    Conditioned Culture Medium
    Fibroblasts
    Wound Healing
    Neoplasms
    Matrix Metalloproteinases
    Gel Chromatography
    Peptide Hydrolases
    Epithelial Cells
    Skin

    Keywords

    • MSF
    • NGAL
    • Lipocalin
    • Keratinocytes
    • Fibroblasts
    • HaCaT
    • Migration inhibitor
    • Wound healing
    • Cancer progression

    Cite this

    Jones, Sarah J. ; Florence, Margaret M. ; Ellis, Ian R. ; Kankova, Katerina ; Schor, Seth L. ; Schor, Ana M. / Co-expression by keratinocytes of migration stimulating factor (MSF) and a functional inhibitor of its bioactivity (MSFI). In: Experimental Cell Research. 2007 ; Vol. 313, No. 20. pp. 4145-4157.
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    abstract = "Migration stimulating factor (MSF) is a potent autocrine and paracrine factor expressed by fibroblasts and epithelial cells in foetal skin, tumours and healing wounds. In tissue culture, MSF bioactivity is present in the conditioned medium of foetal and tumour derived fibroblasts, but not in normal adult fibroblasts or keratinocytes. The conditioned medium of early passage keratinocytes or a keratinocyte line (HaCaT) effectively inhibited the motogenic activity of rhMSF. Fractionation of keratinocyte conditioned medium by size-exclusion chromatography revealed the presence of bioactive MSF as well as a functional inhibitor of MSF (MSFI) in fractions corresponding to approximately 70 kDa and 25 kDa, respectively. MSFI was purified and identified as neutrophil gelatinase-associated lipocalin (NGAL or lipocalin-2). Immunostaining confirmed that keratinocytes expressed both MSF and NGAL, whereas normal adult fibroblasts did not express either. Recombinant and cell-produced NGAL neutralised the motogenic activity of rhMSF. NGAL is known to bind MMP-9 and promote the activity of this protease. In contrast, there was no evidence of NGAL-MSF binding in keratinocyte conditioned medium. MSF displays a number of bioactivities of relevance to cancer progression and wound healing. Our findings indicate a novel function of NGAL and a possible mechanism for regulating MSF activity in tissues.",
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    Co-expression by keratinocytes of migration stimulating factor (MSF) and a functional inhibitor of its bioactivity (MSFI). / Jones, Sarah J.; Florence, Margaret M.; Ellis, Ian R.; Kankova, Katerina; Schor, Seth L.; Schor, Ana M.

    In: Experimental Cell Research, Vol. 313, No. 20, 2007, p. 4145-4157.

    Research output: Contribution to journalArticle

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    AU - Jones, Sarah J.

    AU - Florence, Margaret M.

    AU - Ellis, Ian R.

    AU - Kankova, Katerina

    AU - Schor, Seth L.

    AU - Schor, Ana M.

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    N2 - Migration stimulating factor (MSF) is a potent autocrine and paracrine factor expressed by fibroblasts and epithelial cells in foetal skin, tumours and healing wounds. In tissue culture, MSF bioactivity is present in the conditioned medium of foetal and tumour derived fibroblasts, but not in normal adult fibroblasts or keratinocytes. The conditioned medium of early passage keratinocytes or a keratinocyte line (HaCaT) effectively inhibited the motogenic activity of rhMSF. Fractionation of keratinocyte conditioned medium by size-exclusion chromatography revealed the presence of bioactive MSF as well as a functional inhibitor of MSF (MSFI) in fractions corresponding to approximately 70 kDa and 25 kDa, respectively. MSFI was purified and identified as neutrophil gelatinase-associated lipocalin (NGAL or lipocalin-2). Immunostaining confirmed that keratinocytes expressed both MSF and NGAL, whereas normal adult fibroblasts did not express either. Recombinant and cell-produced NGAL neutralised the motogenic activity of rhMSF. NGAL is known to bind MMP-9 and promote the activity of this protease. In contrast, there was no evidence of NGAL-MSF binding in keratinocyte conditioned medium. MSF displays a number of bioactivities of relevance to cancer progression and wound healing. Our findings indicate a novel function of NGAL and a possible mechanism for regulating MSF activity in tissues.

    AB - Migration stimulating factor (MSF) is a potent autocrine and paracrine factor expressed by fibroblasts and epithelial cells in foetal skin, tumours and healing wounds. In tissue culture, MSF bioactivity is present in the conditioned medium of foetal and tumour derived fibroblasts, but not in normal adult fibroblasts or keratinocytes. The conditioned medium of early passage keratinocytes or a keratinocyte line (HaCaT) effectively inhibited the motogenic activity of rhMSF. Fractionation of keratinocyte conditioned medium by size-exclusion chromatography revealed the presence of bioactive MSF as well as a functional inhibitor of MSF (MSFI) in fractions corresponding to approximately 70 kDa and 25 kDa, respectively. MSFI was purified and identified as neutrophil gelatinase-associated lipocalin (NGAL or lipocalin-2). Immunostaining confirmed that keratinocytes expressed both MSF and NGAL, whereas normal adult fibroblasts did not express either. Recombinant and cell-produced NGAL neutralised the motogenic activity of rhMSF. NGAL is known to bind MMP-9 and promote the activity of this protease. In contrast, there was no evidence of NGAL-MSF binding in keratinocyte conditioned medium. MSF displays a number of bioactivities of relevance to cancer progression and wound healing. Our findings indicate a novel function of NGAL and a possible mechanism for regulating MSF activity in tissues.

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