title: Migration stimulating factor (MSF): its structure, mode of action and possible function in health and disease.
abstract: We have previously reported that (a) fetal fibroblasts migrate into 3-dimensional collagen matrices to a significantly greater extent that do adult cells, (b) this difference in migratory behaviour results from the secretion by fetal fibroblasts of a "migration stimulating factor" (MSF), and (c) adult fibroblasts retain responsiveness to MSF, this providing the basis of a bioassay for monitoring factor activity. Using a recently modified purification protocol, MSF isolated from fetal fibroblast conditioned medium elutes as a single activity peak in the penultimate Mono Q anion exchange chromatography step. Analysis of this material by SDS-PAGE indicates that it consists of three proteins, one with an apparent molecular mass of 119 kDa and a doublet with molecular masses of approximately 43 and 33 kDa, respectively. Our data suggest that the two proteins comprising the doublet result from the degradation of the larger molecule during the purification procedure. Both the 119 kDa species and lower molecular weight doublet stimulate fibroblast migration (with half maximal activity in the region of 1-10 pg/ml) and contain a structural domain exhibiting significant amino acid sequence homology with the gelatin-binding fragment (GBF) of fibronectin. Bona fide preparations of GBF, obtained by the limited proteolysis of plasma fibronectin, also stimulate the migration of adult fibroblasts in a similar dose-dependent manner to that of MSF. In spite of this similarity, MSF and GBF differ in terms of a number of biological and biochemical parameters, thereby suggesting that MSF is a distinct gene product and not a proteolytic degradation fragment of fibronectin. MSF stimulates the synthesis of a high molecular weight species of hyaluronic acid (HA). Our current data suggest that the observed effect of MSF on cell migration is actually a secondary consequence of the accumulation of this HA in the collagen matrix. TGF-beta is a potent inhibitor of MSF, both in terms of its effects on cell migration and HA synthesis. As MSF is present in wound fluid, we have suggested that the inhibition of MSF activity by TGF-beta may reflect the antagonistic interaction of these two cytokines in the control of the wound healing process. Our recent data indicate that discrete minority subpopulations of MSF-secreting fibroblasts are also present at specific sites in the healthy adult and that these may undergo a transient and local expansion during wound healing.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Cell and Structural Biology, University of Manchester, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Schor
authors.forename: A M
authors.initials: AM
authors.lastname: Grey
authors.forename: I
authors.initials: I
authors.lastname: Ellis
authors.forename: A M
authors.initials: AM
authors.lastname: Schor
authors.forename: B
authors.initials: B
authors.lastname: Coles
authors.forename: R
authors.initials: R
authors.lastname: Murphy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002465:Cell Movement / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology; D005353:Fibronectins / Q000235:genetics; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C067625:FN1 protein, human; D005353:Fibronectins; C033135:gelatin binding protein