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Migration stimulating factor: Biochemical characterization, mode of action and function
Başlık:
Migration stimulating factor: Biochemical characterization, mode of action and function
Yazar:
Ellis, Ian Robert, author.
ISBN:
9780355977745
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (497 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
The migration of adult skin fibroblasts into three-dimensional collagen gels is differentially affected by cell density, with subconfluent cells displaying a significantly elevated level of migration compared to confluent ones. Foetal fibroblasts differ from adult fibroblasts in that they display an elevated level of migration at both subconfluent and confluent cell densities. This difference in behaviour results from the secretion by foetal fibroblasts of a 'migration stimulating factor' (MSF) which is not made by their normal adult counterparts. Subsequent studies indicated that skin fibroblasts obtained from the majority of breast cancer patients are foetal-like in terms of both their migratory phenotype and continued production of MSF. Data from our laboratory has also indicated that MSF is present in wound fluid and may play a role in the normal wound healing response. My thesis has been concerned with (a) the further biochemical characterisation of MSF, (b) an investigation of its mode of action on target adult fibroblasts, and (c) documenting a novel effect of the gelatin binding fragment (GBF) of fibronectin on cell migration, and (d) examining the effects of well-characterized cytokines on fibroblast migration. I have demonstrated that MSF exerts a direct stimulatory effect upon the synthesis of a high molecular weight class of hyaluronate (HA) and that it is the accumulation of this HA in the collagen which appears to be responsible for the observed stimulation of cell migration. Other well known cytokines, such as EGF, TGFalpha, aFGF, bFGF, PDGF and TGFbeta-3, also stimulate cell migration; some, but not all of these cytokines appear to resemble MSF in that their effect upon cell migration appears to be dependent upon HA synthesis. During the course of my thesis research, we obtained amino acid sequence data indicating that MSF contains a domain exhibiting a striking sequence homology with the gelatin-binding fragment of fibronectin. Subsequent studies indicated that GBF (prepared by proteolytic degradation of plasma fibronectin) displayed a potent "cytokinelike" effect upon the migration of subconfluent cells and GBF and MSF differed in a number of other respects as well. Other studies using the cytokine TGFbeta-1 indicated that the elevated migration of adult fibroblasts plated at subconfluent cell density was inhibited; under these conditions, TGFbeta-1 induces a parallel decrease in the synthesis of high molecular weight HA. TGFbeta-1 is a potent antagonist of MSF, effectively blocking its stimulation of cell migration and synthesis of high molecular weight HA when fibroblasts are plated at confluence. The data presented in my thesis are discussed in terms of potential physiologic function of MSF in wound healing and how this may be subverted in cancer pathogenesis.
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(683810.1) | 683810-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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