Bistable switch in migration stimulating factor expression

regulation by the concerted signalling of transforming growth factor-β1 and the extracellular matrix

Seth L Schor, Ian R Ellis, Sarah J. Jones, Anne-Marie Woolston, Ana M Schor

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    5 Citations (Scopus)

    Abstract

    Migration stimulating factor (MSF) is an oncofetal motogenic/angiogenic cytokine constitutively expressed by epithelial and stromal cells in fetal and neoplastic tissues. Fibroblasts derived from healthy adult skin do not express MSF but can be induced to do so by treatment with transforming growth factor-ß1 (TGF-ß1). As the bioactivities of both MSF and TGF-ß1 are modulated by the extracellular matrix, we investigated whether the induction of MSF expression by TGF-ß1 is also matrix dependent. We now report that adult fibroblasts are induced to express MSF by a transient treatment with TGF-ß1 (as short as 2 hr) but only when the cells are adherent to a "wound" matrix, such as denatured type I collagen, fibrin or plastic tissue culture dishes. Unexpectedly, this induction of MSF expression persists unabated for the entire subsequent lifespan of the treated cells in the absence of further TGF-ß1 and irrespective of the substratum. Such "activated" MSF expression may, however, be persistently switched off again by a second transient exposure to TGF-ß1 but this time only when the cells are adherent to a "healthy" matrix of native type I collagen. Significantly, the constitutive expression of MSF by fetal and cancer patient fibroblasts could also be persistently switched off by this means. We conclude that TGF-ß1 may both switch on and switch off MSF expression in a manner critically determined by the nature of the matrix substratum and suggest that this may be a possible mechanism underlying the observed dual functionality of TGF-ß1 as both a tumour suppressor and tumour promoter.
    Original languageEnglish
    Pages (from-to)2024-32
    Number of pages9
    JournalInternational Journal of Cancer
    Volume130
    Issue number9
    DOIs
    Publication statusPublished - 2012

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    Transforming Growth Factors
    Extracellular Matrix
    Fibroblasts
    Collagen Type I
    Stromal Cells
    Fibrin
    Carcinogens
    Neoplasms
    Fetus
    Epithelial Cells
    Cytokines
    Skin
    Wounds and Injuries
    Therapeutics

    Cite this

    @article{dc2eac89b0d24743bb9c575e08d902c3,
    title = "Bistable switch in migration stimulating factor expression: regulation by the concerted signalling of transforming growth factor-β1 and the extracellular matrix",
    abstract = "Migration stimulating factor (MSF) is an oncofetal motogenic/angiogenic cytokine constitutively expressed by epithelial and stromal cells in fetal and neoplastic tissues. Fibroblasts derived from healthy adult skin do not express MSF but can be induced to do so by treatment with transforming growth factor-{\ss}1 (TGF-{\ss}1). As the bioactivities of both MSF and TGF-{\ss}1 are modulated by the extracellular matrix, we investigated whether the induction of MSF expression by TGF-{\ss}1 is also matrix dependent. We now report that adult fibroblasts are induced to express MSF by a transient treatment with TGF-{\ss}1 (as short as 2 hr) but only when the cells are adherent to a {"}wound{"} matrix, such as denatured type I collagen, fibrin or plastic tissue culture dishes. Unexpectedly, this induction of MSF expression persists unabated for the entire subsequent lifespan of the treated cells in the absence of further TGF-{\ss}1 and irrespective of the substratum. Such {"}activated{"} MSF expression may, however, be persistently switched off again by a second transient exposure to TGF-{\ss}1 but this time only when the cells are adherent to a {"}healthy{"} matrix of native type I collagen. Significantly, the constitutive expression of MSF by fetal and cancer patient fibroblasts could also be persistently switched off by this means. We conclude that TGF-{\ss}1 may both switch on and switch off MSF expression in a manner critically determined by the nature of the matrix substratum and suggest that this may be a possible mechanism underlying the observed dual functionality of TGF-{\ss}1 as both a tumour suppressor and tumour promoter.",
    author = "Schor, {Seth L} and Ellis, {Ian R} and Jones, {Sarah J.} and Anne-Marie Woolston and Schor, {Ana M}",
    note = "Copyright {\circledC} 2011 UICC.",
    year = "2012",
    doi = "10.1002/ijc.26213",
    language = "English",
    volume = "130",
    pages = "2024--32",
    journal = "International Journal of Cancer",
    issn = "0020-7136",
    publisher = "Wiley",
    number = "9",

    }

    TY - JOUR

    T1 - Bistable switch in migration stimulating factor expression

    T2 - regulation by the concerted signalling of transforming growth factor-β1 and the extracellular matrix

    AU - Schor, Seth L

    AU - Ellis, Ian R

    AU - Jones, Sarah J.

    AU - Woolston, Anne-Marie

    AU - Schor, Ana M

    N1 - Copyright © 2011 UICC.

    PY - 2012

    Y1 - 2012

    N2 - Migration stimulating factor (MSF) is an oncofetal motogenic/angiogenic cytokine constitutively expressed by epithelial and stromal cells in fetal and neoplastic tissues. Fibroblasts derived from healthy adult skin do not express MSF but can be induced to do so by treatment with transforming growth factor-ß1 (TGF-ß1). As the bioactivities of both MSF and TGF-ß1 are modulated by the extracellular matrix, we investigated whether the induction of MSF expression by TGF-ß1 is also matrix dependent. We now report that adult fibroblasts are induced to express MSF by a transient treatment with TGF-ß1 (as short as 2 hr) but only when the cells are adherent to a "wound" matrix, such as denatured type I collagen, fibrin or plastic tissue culture dishes. Unexpectedly, this induction of MSF expression persists unabated for the entire subsequent lifespan of the treated cells in the absence of further TGF-ß1 and irrespective of the substratum. Such "activated" MSF expression may, however, be persistently switched off again by a second transient exposure to TGF-ß1 but this time only when the cells are adherent to a "healthy" matrix of native type I collagen. Significantly, the constitutive expression of MSF by fetal and cancer patient fibroblasts could also be persistently switched off by this means. We conclude that TGF-ß1 may both switch on and switch off MSF expression in a manner critically determined by the nature of the matrix substratum and suggest that this may be a possible mechanism underlying the observed dual functionality of TGF-ß1 as both a tumour suppressor and tumour promoter.

    AB - Migration stimulating factor (MSF) is an oncofetal motogenic/angiogenic cytokine constitutively expressed by epithelial and stromal cells in fetal and neoplastic tissues. Fibroblasts derived from healthy adult skin do not express MSF but can be induced to do so by treatment with transforming growth factor-ß1 (TGF-ß1). As the bioactivities of both MSF and TGF-ß1 are modulated by the extracellular matrix, we investigated whether the induction of MSF expression by TGF-ß1 is also matrix dependent. We now report that adult fibroblasts are induced to express MSF by a transient treatment with TGF-ß1 (as short as 2 hr) but only when the cells are adherent to a "wound" matrix, such as denatured type I collagen, fibrin or plastic tissue culture dishes. Unexpectedly, this induction of MSF expression persists unabated for the entire subsequent lifespan of the treated cells in the absence of further TGF-ß1 and irrespective of the substratum. Such "activated" MSF expression may, however, be persistently switched off again by a second transient exposure to TGF-ß1 but this time only when the cells are adherent to a "healthy" matrix of native type I collagen. Significantly, the constitutive expression of MSF by fetal and cancer patient fibroblasts could also be persistently switched off by this means. We conclude that TGF-ß1 may both switch on and switch off MSF expression in a manner critically determined by the nature of the matrix substratum and suggest that this may be a possible mechanism underlying the observed dual functionality of TGF-ß1 as both a tumour suppressor and tumour promoter.

    U2 - 10.1002/ijc.26213

    DO - 10.1002/ijc.26213

    M3 - Article

    VL - 130

    SP - 2024

    EP - 2032

    JO - International Journal of Cancer

    JF - International Journal of Cancer

    SN - 0020-7136

    IS - 9

    ER -