Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells.
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.
Schor
Seth L
SL
Unit of Cell and Molecular Biology, The Dental School, University of Dundee, Dundee, Scotland. S.L.Schor@dundee.ac.uk
Ellis
Ian R
IR
Jones
Sarah J
SJ
Baillie
Robin
R
Seneviratne
Kanjula
K
Clausen
Julia
J
Motegi
Katsumi
K
Vojtesek
Borek
B
Kankova
Katerina
K
Furrie
Elizabeth
E
Sales
Mark J
MJ
Schor
Ana M
AM
Kay
Richard A
RA
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D005353:Fibronectins / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism
D016207:Cytokines; D018076:DNA, Complementary; C067625:FN1 protein, human; D005353:Fibronectins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins