Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells

Seth L. Schor, Ian R. Ellis, Sarah J. Jones, Robin Baillie, Kanjula Seneviratne, Julia Clausen, Katsumi Motegi, Borek Vojtesek, Katerina Kankova, Elizabeth Furrie, Mark J. Sales, Ana M. Schor, Richard A. Kay

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    Abstract

    Migration-stimulating factor (MSF) is a 70-kDa motogenic protein previously reported to be expressed by fetal and cancer patient fibroblasts cultured in vitro and present in the serum of breast cancer patients. A 2.2-kb full-length MSF cDNA has been cloned and shown to be a truncated isoform of fibronectin generated from its primary gene transcript by a hitherto unrecognized intron read-through mechanism. MSF cDNA is identical to the 5' end of fibronectin cDNA, up to and including exon III-1a, and terminates in a novel 195-nucleotide 3' sequence. This MSF unique sequence is derived from the intron immediately downstream of exon III-1a in the fibronectin gene and is not found in any previously identified “full-length” fibronectin cDNA. MSF mRNA is 1000-fold less abundant than full-length fibronectin message in fetal fibroblasts and exhibits rapid biphasic decay kinetics previously associated with oncogenes and stress response molecules. MSF recombinant protein exhibits a potent and substratum-dependent motogenic activity, with half-maximal response manifest at 0.1–1.0 pg/ml. This activity is (a) mediated by the IGD amino acid motif; and (b) not expressed by (i.e., cryptic within) full-length fibronectin. In situ hybridization and immunohistochemistry confirm that MSF is expressed by tumor-associated fibroblasts and additionally indicate that it is also expressed by carcinoma cells and tumor-associated vascular endothelial cells. MSF, as a consequence of its potent bioactivities and expression by both stromal and carcinoma cell populations, is well placed to function as an epigenetic effector promoting cancer development.
    Original languageEnglish
    Pages (from-to)8827-8836
    Number of pages10
    JournalCancer Research
    Volume63
    Issue number24
    Publication statusPublished - 2003

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    Stromal Cells
    Fibronectins
    Protein Isoforms
    Carcinoma
    Complementary DNA
    Neoplasms
    Introns
    Exons
    Fibroblasts
    Amino Acid Motifs
    Oncogenes
    Recombinant Proteins
    Epigenomics
    Genes
    In Situ Hybridization
    Endothelial Cells
    Immunohistochemistry
    Breast Neoplasms
    Messenger RNA
    Serum

    Cite this

    Schor, Seth L. ; Ellis, Ian R. ; Jones, Sarah J. ; Baillie, Robin ; Seneviratne, Kanjula ; Clausen, Julia ; Motegi, Katsumi ; Vojtesek, Borek ; Kankova, Katerina ; Furrie, Elizabeth ; Sales, Mark J. ; Schor, Ana M. ; Kay, Richard A. / Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells. In: Cancer Research. 2003 ; Vol. 63, No. 24. pp. 8827-8836.
    @article{7e7ff31bc40841878c7fa4656154794d,
    title = "Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells",
    abstract = "Migration-stimulating factor (MSF) is a 70-kDa motogenic protein previously reported to be expressed by fetal and cancer patient fibroblasts cultured in vitro and present in the serum of breast cancer patients. A 2.2-kb full-length MSF cDNA has been cloned and shown to be a truncated isoform of fibronectin generated from its primary gene transcript by a hitherto unrecognized intron read-through mechanism. MSF cDNA is identical to the 5' end of fibronectin cDNA, up to and including exon III-1a, and terminates in a novel 195-nucleotide 3' sequence. This MSF unique sequence is derived from the intron immediately downstream of exon III-1a in the fibronectin gene and is not found in any previously identified “full-length” fibronectin cDNA. MSF mRNA is 1000-fold less abundant than full-length fibronectin message in fetal fibroblasts and exhibits rapid biphasic decay kinetics previously associated with oncogenes and stress response molecules. MSF recombinant protein exhibits a potent and substratum-dependent motogenic activity, with half-maximal response manifest at 0.1–1.0 pg/ml. This activity is (a) mediated by the IGD amino acid motif; and (b) not expressed by (i.e., cryptic within) full-length fibronectin. In situ hybridization and immunohistochemistry confirm that MSF is expressed by tumor-associated fibroblasts and additionally indicate that it is also expressed by carcinoma cells and tumor-associated vascular endothelial cells. MSF, as a consequence of its potent bioactivities and expression by both stromal and carcinoma cell populations, is well placed to function as an epigenetic effector promoting cancer development.",
    author = "Schor, {Seth L.} and Ellis, {Ian R.} and Jones, {Sarah J.} and Robin Baillie and Kanjula Seneviratne and Julia Clausen and Katsumi Motegi and Borek Vojtesek and Katerina Kankova and Elizabeth Furrie and Sales, {Mark J.} and Schor, {Ana M.} and Kay, {Richard A.}",
    note = "dc.publisher: American Association for Cancer Research Flagship paper reporting the cloning and identification of MSF as a genetically truncated isoform of fibronectin, the first such isoform of human fibronectin to be described . Presents in vitro mutagenesis data indicating that the potent motogenic activity of MSF is mediated by its constituent IGD motifs.",
    year = "2003",
    language = "English",
    volume = "63",
    pages = "8827--8836",
    journal = "Cancer Research",
    issn = "0008-5472",
    publisher = "American Association for Cancer Research",
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    }

    Schor, SL, Ellis, IR, Jones, SJ, Baillie, R, Seneviratne, K, Clausen, J, Motegi, K, Vojtesek, B, Kankova, K, Furrie, E, Sales, MJ, Schor, AM & Kay, RA 2003, 'Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells', Cancer Research, vol. 63, no. 24, pp. 8827-8836.

    Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells. / Schor, Seth L.; Ellis, Ian R.; Jones, Sarah J.; Baillie, Robin; Seneviratne, Kanjula; Clausen, Julia; Motegi, Katsumi; Vojtesek, Borek; Kankova, Katerina; Furrie, Elizabeth; Sales, Mark J.; Schor, Ana M.; Kay, Richard A.

    In: Cancer Research, Vol. 63, No. 24, 2003, p. 8827-8836.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells

    AU - Schor, Seth L.

    AU - Ellis, Ian R.

    AU - Jones, Sarah J.

    AU - Baillie, Robin

    AU - Seneviratne, Kanjula

    AU - Clausen, Julia

    AU - Motegi, Katsumi

    AU - Vojtesek, Borek

    AU - Kankova, Katerina

    AU - Furrie, Elizabeth

    AU - Sales, Mark J.

    AU - Schor, Ana M.

    AU - Kay, Richard A.

    N1 - dc.publisher: American Association for Cancer Research Flagship paper reporting the cloning and identification of MSF as a genetically truncated isoform of fibronectin, the first such isoform of human fibronectin to be described . Presents in vitro mutagenesis data indicating that the potent motogenic activity of MSF is mediated by its constituent IGD motifs.

    PY - 2003

    Y1 - 2003

    N2 - Migration-stimulating factor (MSF) is a 70-kDa motogenic protein previously reported to be expressed by fetal and cancer patient fibroblasts cultured in vitro and present in the serum of breast cancer patients. A 2.2-kb full-length MSF cDNA has been cloned and shown to be a truncated isoform of fibronectin generated from its primary gene transcript by a hitherto unrecognized intron read-through mechanism. MSF cDNA is identical to the 5' end of fibronectin cDNA, up to and including exon III-1a, and terminates in a novel 195-nucleotide 3' sequence. This MSF unique sequence is derived from the intron immediately downstream of exon III-1a in the fibronectin gene and is not found in any previously identified “full-length” fibronectin cDNA. MSF mRNA is 1000-fold less abundant than full-length fibronectin message in fetal fibroblasts and exhibits rapid biphasic decay kinetics previously associated with oncogenes and stress response molecules. MSF recombinant protein exhibits a potent and substratum-dependent motogenic activity, with half-maximal response manifest at 0.1–1.0 pg/ml. This activity is (a) mediated by the IGD amino acid motif; and (b) not expressed by (i.e., cryptic within) full-length fibronectin. In situ hybridization and immunohistochemistry confirm that MSF is expressed by tumor-associated fibroblasts and additionally indicate that it is also expressed by carcinoma cells and tumor-associated vascular endothelial cells. MSF, as a consequence of its potent bioactivities and expression by both stromal and carcinoma cell populations, is well placed to function as an epigenetic effector promoting cancer development.

    AB - Migration-stimulating factor (MSF) is a 70-kDa motogenic protein previously reported to be expressed by fetal and cancer patient fibroblasts cultured in vitro and present in the serum of breast cancer patients. A 2.2-kb full-length MSF cDNA has been cloned and shown to be a truncated isoform of fibronectin generated from its primary gene transcript by a hitherto unrecognized intron read-through mechanism. MSF cDNA is identical to the 5' end of fibronectin cDNA, up to and including exon III-1a, and terminates in a novel 195-nucleotide 3' sequence. This MSF unique sequence is derived from the intron immediately downstream of exon III-1a in the fibronectin gene and is not found in any previously identified “full-length” fibronectin cDNA. MSF mRNA is 1000-fold less abundant than full-length fibronectin message in fetal fibroblasts and exhibits rapid biphasic decay kinetics previously associated with oncogenes and stress response molecules. MSF recombinant protein exhibits a potent and substratum-dependent motogenic activity, with half-maximal response manifest at 0.1–1.0 pg/ml. This activity is (a) mediated by the IGD amino acid motif; and (b) not expressed by (i.e., cryptic within) full-length fibronectin. In situ hybridization and immunohistochemistry confirm that MSF is expressed by tumor-associated fibroblasts and additionally indicate that it is also expressed by carcinoma cells and tumor-associated vascular endothelial cells. MSF, as a consequence of its potent bioactivities and expression by both stromal and carcinoma cell populations, is well placed to function as an epigenetic effector promoting cancer development.

    M3 - Article

    VL - 63

    SP - 8827

    EP - 8836

    JO - Cancer Research

    JF - Cancer Research

    SN - 0008-5472

    IS - 24

    ER -