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 - Dec 2003

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  • Cite this

    Schor, S. L., Ellis, I. R., Jones, S. J., Baillie, R., Seneviratne, K., Clausen, J., Motegi, K., Vojtesek, B., Kankova, K., Furrie, E., Sales, M. J., Schor, A. M., & Kay, R. A. (2003). Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells. Cancer Research, 63(24), 8827-8836. http://cancerres.aacrjournals.org/content/63/24/8827.full