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M Perryman

Publications and source records attributed to M Perryman.

7 recordsLinked to original sources

Epithelial scatter factor and development of the chick embryonic axis.

Scatter factor, a recently characterised protein secreted by certain embryonic fibroblasts, affects cultured epithelial by increasing cell motility, the breakdown of cell junctions and cell scattering. The process of gastrulation in higher vertebrate embryos, during which the primitive streak forms, involves an epithelial-to-mesenchymal transformation resembling the effects of the factor on cultured cells. The factor was applied locally to chick embryos, using both scatter-factor-secreting cell lines and inert carriers. We found that scatter factor can generate local supernumerary axial structures resembling primitive streak and/or neural plate and conclude that it may have primitive-streak and/or neural-inducing activity in chick embryos.

Animals↗

Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement.

Scatter factor is a fibroblast-derived protein that causes separation of contiguous epithelial cells and increased local mobility of unanchored cells. Highly purified scatter factor has been obtained by a combination of ion-exchange and reverse-phase chromatography from serum-free medium conditioned by a ras-transformed clone (D4) of mouse NIH 3T3 fibroblasts. Under nonreducing conditions scatter factor has a pI of approximately 9.5 and migrates in SDS/polyacrylamide gels as a single band at approximately 62 kDa from which epithelial scatter activity can be recovered. Treatment with reducing agents destroys biological activity and is associated with the appearance of two major bands at approximately 57 and approximately 30 kDa. Whether both the 57-kDa and 30-kDa polypeptides are required for biological activity remains to be established. All the activities observed in crude medium conditioned by cells producing scatter factor are retained by highly purified preparations of scatter factor. These include (i) increased local movement, modulation of morphology, and inhibition of junction formation by single epithelial cells and (ii) disruption of epithelial interactions and cell scattering from preformed epithelial sheets. These changes occur with picomolar concentrations of purified scatter factor and without an effect on cell growth.

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An epithelial scatter factor released by embryo fibroblasts.

Medium conditioned by human embryo fibroblasts breaks structural junctions between several types of epithelial cells, leading to separation and scattering of the cells. An assay developed in MDCK cells shows activity up to a dilution of at least 1 in 64, equivalent to less than 100 ng of total protein. The activity is non-dialysable, heat-labile, and sensitive to trypsin, and it is assumed to be due to one or more proteins. After addition of the factor, separation of MDCK cells begins in about 15 min and is complete in 10 h. It increases migration of MDCK cells into wounds, and causes collapse of domes. Locomotion of isolated cells is not enhanced, but cell shape is affected by local membrane movement. Under the culture conditions used the factor, or an associated protein, causes a weak inhibition of cell growth without cytotoxic activity. The scattering factor has not been purified, nor has a physiological role been identified, but it might be concerned in the mobilization of epithelial cells.

Animals↗

Cultures of exfoliated mammary epithelial cells: variation between donors.

Human milk contains clonogenic epithelial cells which give rise to three distinct colony types, namely, joined elongated, joined cuboidal, and open (i.e. unjoined). Previous studies have shown that these may be interrelated and may reflect stages in cell differentiation in the human mammary gland. This paper reports an analysis of paired milk samples from a series of donors, and shows that the predominant clonogenic cell type varies from donor to donor. This could reflect individual variation in the cell population of the lactating human breast.

Africa↗

Studies on differentiation of human mammary epithelial cells in culture: distinctive specificities of conditioned media.

Epithelium cultured from human milk contains cells of two types distinguishable by morphology and keratin pattern. First, the "open" type comprises cells which are isolated from one another, and which do not form typical epithelial sheets. Second, the "joined" type grow as tightly adjoining cell sheets. Clonal analysis shows that open cells, besides reproducing the same phenotype, can give rise to mixed colonies containing joined cells, thus indicating a pathway of in vitro differentiation. When conditioned medium was used to enhance colony growth it was found that human embryo lung fibroblasts release an activity which specifically enhances the open type of mammary epithelial cell. On the contrary the Nil 8 hamster fibroblast line and certain other cells release activities which primarily affect the joined cell type. This suggests that there are naturally occurring factors with specificities for distinct stages in mammary epithelial cell differentiation.

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Clonal analysis of morphological phenotype in cultured mammary epithelial cells from human milk.

Three main types of colony forming epithelial cell, termed elongated, cuboidal and open, are found in cultures of human milk. Subculture of identified colonies, and cloning from single cells shows that each cell type can maintain its morphological phenotype, but in addition the cuboidal and open cell types can give rise to the elongated type. The results, which suggest a differentiation pathway starting with open cell types, are discussed in relation to differentiation studies on mammary cancer cells.

Breast↗

Scatter factor is a fibroblast-derived modulator of epithelial cell mobility.

Various factors are known to regulate cell growth and differentiation, but less is known of agents which affect movement and positioning, particularly in epithelial-mesenchymal interactions. Cultured human embryo fibroblasts release a protein with a relative molecular mass (Mr) of approximately 50,000 (50K) that affects epithelial cells by causing a disruption of junctions, an increase in local motility and a scattering of contiguous sheets of cells. To investigate specificity, a range of cells has been examined for the ability to produce the factor and for sensitivity to its action. Most freshly isolated normal epithelia and epithelia from cell lines of normal tissue, but not epithelia from tumour cell lines or fibroblasts, were sensitive to scatter factor. In contrast, production of the factor, as identified by activity and by chromatography, was restricted to embryonic fibroblasts and certain variants of 3T3 and BHK21 cells and their transformed derivatives. We conclude that the scatter factor is a paracrine effector of epithelial-mesenchymal interaction, which affects the intercellular connections and mobility of normal epithelial cells. The factor might be involved in epithelial migration, such as occurs in embryogenesis or wound healing.

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