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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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",
month = "12",
language = "English",
volume = "63",
pages = "8827--8836",
journal = "Cancer Research",
issn = "0008-5472",
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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, 12.2003, p. 8827-8836.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Migration-stimulating factor

T2 - 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 - 2003/12

Y1 - 2003/12

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 -