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P Dowrick

Publications and source records attributed to P Dowrick.

5 recordsLinked to original sources
PubMed1993

Cytoskeletal changes associated with cell motility.

This chapter reviews various aspects of changes in cytoskeletal organization which occur upon activating a highly motile cell phenotype. The first of these relates to the rapid formation of F-actin-rich ruffles on the apical cell surfaces following the addition of one of several motility factors. In a number of aspects these ruffles resemble leading edge lamellipodia. The ruffles form upon ligand binding and, at least for one cytokine, the receptors become associated with the ruffles. For several cytokines the ruffles are circular and in all cases they are associated with much increased pinocytosis. The possible significance is considered of these very early markers of a motile cell phenotype. A second topic covered is the role of microtubules (MTs) in maintaining cell polarity in some cell types but not others. The micro-injection of biotin-tubulin into cells has provided a valuable marker of MT turnover. Using this method it has been found that the microtubule network in secondary chick heart fibroblasts (2 degrees CHFs), where MTs are required to maintain a polarized motility, does not turn over significantly more slowly than in 1 degree CHFs which do not require an intact MT network for locomotion. In both cases the MT network turns over very quickly and no sub-population of longer-lived MTs has been found. In contrast, in motile epithelial (PtK2) cells, a sub-population of longer-lived microtubules has been identified and these appear to maintain the long cell processes.

Animals↗
PubMed1993

Circular ruffle formation and closure lead to macropinocytosis in hepatocyte growth factor/scatter factor-treated cells.

Treatment with hepatocyte growth factor/scatter factor (HGF/SF) rapidly induced the formation of conspicuous circular ruffles on the apical surfaces of two kidney cell lines, MDCK and PtK2. The ruffles were found to contain significant amounts of F-actin and myosin as judged by immunofluorescence microscopy. Time-lapse photomicroscopy demonstrated that the ruffles constrict, closing over, and were followed by the formation of phase bright structures. That these structures were macropinocytotic vesicles was confirmed using fluorescein isothiocyanate (FITC)-dextran as a marker for fluid uptake. It is hypothesized that the constriction of the ruffles followed by membrane fusion causes the vesicles to form. Treatment with suramin blocked both circular ruffle formation and scattering, suggesting that ligand binding was the causal agent for ruffle formation. The drugs amiloride and SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid) also completely inhibited ruffle formation, suggesting that ion transport was an early consequence of HGF/SF binding and that these transport effects had a major role in the cytoskeletal changes leading to circular ruffle formation. The appearance of macropinocytotic vesicles was also blocked by amiloride treatment. Surprisingly though, subsequent scattering was not blocked by amiloride treatment, although suramin and SITS both entirely inhibited scattering.

3T3 Cells↗
PubMed1992

The presence of scatter factor in patients with metastatic spread to the pleura.

Pleural effusion fluid obtained from eleven patients with metastatic spread to the pleura was screened for the ability to cause the dispersal--'scattering'--of MDCK colonies in vitro. Four of these samples proved to be positive using this assay. Of these two had titres high enough to warrant further purification on a cation exchange Mono S column. Active material from both lung samples, eluted at the same positions as factor from cultured human lung fibroblasts (MRC-5) and human placenta but in a slightly different position to murine scatter factor. In both cases the semi-purified active agent was identified as hepatocyte growth factor/scatter factor (HGF/SF) using an ELISA detection system specific for human HGF/SF. This is the first report identifying the presence of significant amounts of HGF/SF in the pleura of patients where malignant spread has occurred.

Animals↗