Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cell migration”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1999

Developmental regulation of cell migration. Insight from a genetic approach in Drosophila.

Cell movements are fascinating and dramatic features of normal animal development. Moreover, failures in cell migration can lead to birth defects, and inappropriate cell migration can lead to cancer metastasis. Genetic approaches are beginning to provide some insights into the molecular basis for the developmental regulation of cell migration. This review discusses the progress that has been made in understanding the regulation of cell migration during Drosophila development, using a molecular genetic approach. In particular, these studies have implicated signaling through a receptor tyrosine kinase in the spatial control of migration. Reorganization of the cytoskeleton, under the control of the guanosine triphosphatase, Rac, is also critical for cell migration. Finally, genetic studies have demonstrated that the timing of cell migration is under transcriptional control.

Animals↗
PubMedDate not supplied

New FDA migration cell used to study migration of styrene from polystyrene into various solvents.

A new cell was evaluated for studying the migration of components of plastic food packaging materials into various food simulating solvents. Data obtained using this cell to study the migration of styrene from polystyrene at 40 and 70 degrees C are presented. Food simulating solvents tested were: water; 3% acetic acid; 8, 20, 50, and 100% ethanol; corn oil; HB-307; heptane; hexadecane; and decanol. An iterative Basic computer program is described that fits the migration vs time data obtained to mathematical models, based on Ficks' law, yielding migrant/polymer diffusion coefficients (Dp). Dp values determined for styrene migration from polystyrene at 40 and 70 degrees C were 3 X 10(-13) and 4 X 10(-12) sq. cm/s, respectively.

Chemical Phenomena↗
PubMed2001

ribbon encodes a novel BTB/POZ protein required for directed cell migration in Drosophila melanogaster.

During development, directed cell migration is crucial for achieving proper shape and function of organs. One well-studied example is the embryonic development of the larval tracheal system of Drosophila, in which at least four signaling pathways coordinate cell migration to form an elaborate branched network essential for oxygen delivery throughout the larva. FGF signaling is required for guided migration of all tracheal branches, whereas the DPP, EGF receptor, and Wingless/WNT signaling pathways each mediate the formation of specific subsets of branches. Here, we characterize ribbon, which encodes a BTB/POZ-containing protein required for specific tracheal branch migration. In ribbon mutant tracheae, the dorsal trunk fails to form, and ventral branches are stunted; however, directed migrations of the dorsal and visceral branches are largely unaffected. The dorsal trunk also fails to form when FGF or Wingless/WNT signaling is lost, and we show that ribbon functions downstream of, or parallel to, these pathways to promote anterior-posterior migration. Directed cell migration of the salivary gland and dorsal epidermis are also affected in ribbon mutants, suggesting that conserved mechanisms may be employed to orient cell migrations in multiple tissues during development.

Amino Acid Sequence↗
PubMed2000

CB1 cannabinoid receptor-mediated cell migration.

Recent studies have suggested that cell migratory responses are often mediated by G(i) protein-coupled receptors. Because it is known that CB1 cannabinoid receptors are coupled to pertussis toxin-sensitive G proteins, we proposed that CB1 may mediate cell migration. To test this hypothesis, modified Boyden chamber assays were used to investigate cell migration mediated by CB1 cannabinoid receptors. HU-210, WIN55212-2, and anandamide, three cannabinoid agonists with distinct chemical structures, induced migration of human embryonic kidney 293 cells stably transfected with human CB1 gene, but not 293 cells transfected with an empty expression vector. These migratory responses were concentration-dependent. The EC(50) values for HU-210, WIN55212-2, and anandamide were 0.19 +/- 0.04, 12. 2 +/- 1.4, and 39.9 +/- 3.7 nM, respectively. The maximal migration index for HU-210, WIN55212-2, and anandamide were 8.9 +/- 1.6, 9.5 +/- 1.6, and 8.8 +/- 1.3, respectively. Pretreating cells with 100 ng/ml pertussis toxin eliminated the cannabinoid agonist-induced cell migration. SR141716A, a selective antagonist for CB1, inhibited the cannabinoid agonist-induced migratory responses in a concentration-dependent manner. Checkerboard analysis demonstrated that anandamide-induced cell migrations are due to chemotaxis as well as chemokinesis. Furthermore, anandamide-induced migratory responses were inhibited, in a concentration-dependent manner, by PD098059, an inhibitor of mitogen-activated protein kinase activation, but not by 8-bromoadenosine-3',5'-cyclic monophosphate, a cell-permeable cAMP analog. These data demonstrate that cannabinoid agonists are able to induce chemotaxis and chemokinesis, and that these migratory responses are mediated by G protein-coupled, CB1 cannabinoid receptors. In addition, these data suggest that activation of mitogen-activated protein kinase plays an important role, whereas inhibition of adenylate cyclase is probably not involved in the cell migration mediated by CB1.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2006

Sphingosine-1-phosphate inhibits cell migration and endothelial to mesenchymal cell transformation during cardiac development.

Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid metabolite that exerts important effects on numerous cellular events via cell surface receptors, S1P(1-5). S1P influences differentiation, proliferation, and migration during vascular development. However, the effects of S1P signaling on early cardiac development are not well understood. To address this issue, we examined the expression of S1P regulatory enzymes and S1P receptors during cardiac development. We observed that enzymes that regulate S1P levels, sphingosine kinase and sphingosine-1-phosphate phosphatase, are expressed in the developing heart. In addition, RT-PCR revealed that four of the five known S1P receptors (S1P(1-4)) are also expressed in the developing heart. Next, effects of altered S1P levels on whole embryo and atrioventricular (AV) canal cultures were investigated. We demonstrate that inactivation of the S1P producing enzyme, sphingosine kinase, leads to cell death in cardiac tissue which is rescued by exogenous S1P treatment. Other experiments reveal that increased S1P concentration prevents alterations in cell morphology that are required for cell migration. This effect results in reduced cell migration and inhibited mesenchymal cell formation in AV canal cushion tissue. These data indicate that S1P, locally maintained within a specific concentration range, is an important and necessary component of early heart development.

Animals↗
PubMed2000

Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling.

Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). NEP substrates such as bombesin and endothelin-1 induce cell migration. We investigated the mechanisms of NEP regulation of cell migration in PC cells, including regulation of phosphorylation on tyrosine of focal adhesion kinase (FAK). Western analyses and cell migration assays revealed an inverse correlation between NEP expression and the levels of FAK phosphorylation and cell migration in PC cell lines. Constitutively expressed NEP, recombinant NEP, and induced NEP expression using a tetracycline-repressive expression system inhibited bombesin- and endothelin-1-stimulated FAK phosphorylation and cell migration. This results from NEP-induced inhibition of neuropeptide-stimulated association of FAK with cSrc protein. Expression of a mutated catalytically inactive NEP protein also resulted in partial inhibition of FAK phosphorylation and cell migration. Coimmunoprecipitation experiments show that NEP associates with tyrosine-phosphorylated Lyn kinase, which then binds the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in an NEP-Lyn-PI3-K protein complex. This complex competitively blocks FAK-PI3-K interaction, suggesting that NEP protein inhibits cell migration via a protein-protein interaction independent of its catalytic function. These experiments demonstrate that NEP can inhibit FAK phosphorylation on tyrosine and PC cell migration through multiple pathways and suggest that cell migration which contributes to invasion and metastases in PC cells can be regulated by NEP.

Animals↗
PubMed2002

The impact of c-met/scatter factor receptor on dendritic cell migration.

Dendritic cells (DC) are professional antigen-presenting cells that possess both migratory properties and potent T cell stimulatory activity, and that allow the uptake of antigenic material inperipheral tissues and its subsequent presentation in the T cell areas of lymphoid organs. Thus motility represents a central property that is required for DC function. Here we report on the expression of the receptor tyrosine kinase c-met in DC. c-Met is the high affinity receptor for scatter factor (SF)/hepatocyte growth factor, and ligand-activated c-met exhibits mitogenic, morphogenic andmotogenic activity in vivo and in vitro. c-Met is signaling competent in DC since it is effectively tyrosine phosphorylated in response to SF ligand. It is demonstrated here that ligand-activated c-met regulates DC adhesion to the extracellular matrix component laminin but leaves antigen presenting function unaffected. Importantly, in ear sheet explant experiments activationof c-met by ligand induces emigration of cutaneous DC (Langerhans cell, LC) from skin, but SF is not a chemoattractant factor for DC. Our results suggest an important role of the c-met/SF system in DC/LC migration.

Animals↗
PubMed2004

Role of reactive oxygen species in inhibition of endothelial cell migration by oxidized low-density lipoprotein.

OBJECTIVE: Endothelial cell migration is inhibited by oxidized low-density lipoprotein (oxLDL) and lysophosphatidylcholine (lysoPC). The purpose of this study was to explore the mechanism of this inhibition, specifically the role of reactive oxygen species. METHODS: The ability of oxLDL, lysoPC, and known superoxide generators to stimulate endothelial cell production of reactive oxygen species and inhibit endothelial cell migration under the same conditions was assessed. Reactive oxygen species production was assessed with dichlorofluorescein. Migration was studied with a razor scrape assay and measured after 24 hours. In addition, the ability of various antioxidants, added before initiation of the scrape assay, to restore endothelial cell migration in oxLDL was determined. RESULTS: OxLDL and lysoPC, at concentrations that stimulated reactive oxygen species production, also inhibited endothelial cell migration. Other agents that generated superoxide also inhibited endothelial cell migration, but hydrogen peroxide did not. Of a variety of antioxidants assessed for their ability to preserve endothelial cell migration in the presence of oxLDL, only superoxide dismutase and reduced nicotinamide adenine dinucleotide (phosphate) oxidase inhibitors (diphenyleneiodonium, quinacrine, hydralazine) preserved endothelial cell migration. CONCLUSIONS: These data suggest that oxLDL inhibits endothelial cell migration through a superoxide-dependent mechanism and that reduced nicotinamide adenine dinucleotide (phosphate) oxidase is the cellular source of the superoxide. CLINICAL RELEVANCE: OxLDL inhibits endothelial cell migration, and may impair healing of arterial injuries. The mechanism of oxidized LDL inhibition is not known. Our in vitro studies show that the inhibitory properties are related to production of reactive oxygen species. Superoxide dismutase or inhibitors of reduced nicotinamide adenine dinucleotide phosphate oxidase can preserve endothelial migration in the presence of oxLDL. This might improve the healing of endothelial injuries at sites of arterial repair or angioplasty, especially in lipid-laden arterial walls.

Animals↗
PubMed1993

Photoinhibition of smooth muscle cell migration: potential therapy for restenosis.

Evidence from animal, autopsy, and atherectomy studies demonstrates that migration and proliferation of smooth muscle cells of medial origin result in neointima formation and decreased luminal cross-sectional area. The purpose of this study was to evaluate whether low energy light irradiation can inhibit smooth muscle cell migration and therefore potentially reduce the degree of neointima formation and the incidence of restenosis. The migration kinetics of bovine aortic smooth muscle cell monolayers were examined using a fence assay. The effect on smooth muscle cell migration of irradiation with monochromatic light at wave-lengths ranging from 400 to 700 nm was compared to the migration of cells irradiated with broadband white light or maintained in the dark. Wavelength specific photoinhibition of smooth muscle cell migration was observed; 594-600 nm light reproducibly inhibited migration by 12-29% (P < 0.05). Migration rate was significantly reduced following daily radiant exposures of 1.0 J/cm2 as well as following a single radiant exposure of 0.09 or 0.9 J/cm2. The decrease in migration was not associated with any change in cell proliferation or [3H] thymidine incorporation. We conclude that 594-600 nm light inhibits smooth muscle cell migration in vitro and may potentially be used in vivo to decrease fibrointimal thickening following arterial injury. This application of photoinhibition may be useful in retarding restenosis following angioplasty.

Animals↗
PubMed2001

Aldehyde fixation of thiol-reactive fluorescent cytoplasmic probes for tracking cell migration.

Tracking of cell migration plays an important role in the study of morphogenesis, inflammation, and metastasis. The recent development of probes that exist as intracellular peptide-fluorescence dye adducts has offered the possibility of aldehyde fixation of these dyes for detailed anatomic studies of lymphocyte trafficking. To define the conditions for fixation of these cytoplasmic fluorescent probes, we compared fixation conditions containing formaldehyde, glutaraldehyde, paraformaldehyde, zinc formaldehyde, and glyoxylate, as well as fixation by quick-freezing in liquid nitrogen-cooled methylbutane. The efficacy of aldehyde fixation of the cell fluorescence was assessed by quantitative tissue cytometry and flow cytometry. We studied cytoplasmic fluorescent dyes with discrete emissions in the green [5-chloromethylfluorescein diacetate (CMFDA); 492 ex, 516 em] and orange [5-(and-6)-(4-chloromethyl(benzoyl)amino) tetramethylrhodamine (CMTMR); 540 ex, 566 em] spectra. The results demonstrated that aldehyde fixation preserved cell fluorescence for more than 6 months. The primary difference between the aldehyde fixatives was variability in the difference between the yield of the cell fluorescence and the relevant background fluorescence. Formaldehyde and paraformaldehyde were superior to the other fixatives in preserving cell fluorescence while limiting background fluorescence. With these fixatives, both the CMFDA and CMTMR fluorescent dyes permitted sufficient anatomic resolution for reliable localization in long-term cell tracking studies.

Aldehydes↗
PubMed1998

Gene expression of monocyte chemoattractant protein-1 in giant cell tumors of bone osteoclastoma: possible involvement in CD68+ macrophage-like cell migration.

Giant cell tumor of bone (GCT) is one of a few neoplasms in which the macrophage/osteoclast precursor cells and osteoclast-like giant cells infiltrate the tumor mass. Monocyte chemoattractant protein 1 (MCP-1) is a potent chemotactic factor specific for monocytes. In search of relevant cytokines that may enhance the recruitment of these reactive cells, we evaluated the localization and regulation of MCP-1 mRNA and protein in GCT by using Northern blot analysis, in situ hybridization and immunohistochemistry. We also determined whether conditioned medium obtained from GCT cultures can recruit human peripheral blood monocytes (CD68+) in an in vitro chemotactic assay. Using Northern blot analysis, we detected the specific gene transcript for MCP-1 in all GCT samples tested. In situ hybridization and immunohistochemistry revealed that both MCP-1 gene transcript and protein were consistently present in the cytoplasm of stromal-like tumor cells of GCT. Treatment of mononuclear cells from GCT at third passage with TGF-beta1 for 24 h increased the level of MCP-1 mRNA in a dose-dependent manner, with the maximum effect at 1 ng/ml. Conditioned media from GCT cultures promoted the chemotactic migration of CD68+ peripheral monocytes, an activity which was abolished by the addition of MCP-1 antibody to the conditioned medium. Thus, the results of this study suggest that recruitment of CD68+ macrophage-like cells may be due to the production MCP-1 by stromal-like tumor cells. These CD68+ cells may originate from peripheral blood and could have the capability of further differentiating into osteoclasts in the tumor.

Antigens, CD↗
PubMed2005

Subcellular targeting of oxidants during endothelial cell migration.

Endogenous oxidants participate in endothelial cell migration, suggesting that the enzymatic source of oxidants, like other proteins controlling cell migration, requires precise subcellular localization for spatial confinement of signaling effects. We found that the nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase adaptor p47(phox) and its binding partner TRAF4 were sequestered within nascent, focal complexlike structures in the lamellae of motile endothelial cells. TRAF4 directly associated with the focal contact scaffold Hic-5, and the knockdown of either protein, disruption of the complex, or oxidant scavenging blocked cell migration. An active mutant of TRAF4 activated the NADPH oxidase downstream of the Rho GTPases and p21-activated kinase 1 (PAK1) and oxidatively modified the focal contact phosphatase PTP-PEST. The oxidase also functioned upstream of Rac1 activation, suggesting its participation in a positive feedback loop. Active TRAF4 initiated robust membrane ruffling through Rac1, PAK1, and the oxidase, whereas the knockdown of PTP-PEST increased ruffling independent of oxidase activation. Our data suggest that TRAF4 specifies a molecular address within focal complexes that is targeted for oxidative modification during cell migration.

Cell Movement↗
PubMed2006

Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth.

Cell migration is central to development and post-traumatic regeneration. The differential increase in 6-sulphated chondroitins during axonal growth in both crushed sciatic nerves and brain development suggests that chondroitin 6-sulphotransferase-1 (C6ST-1) is a key enzyme that mediates cell migration in the process. We have cloned the cDNA of the C6ST-1 gene (C6st1) (GenBank accession number AF178689) from crushed sciatic nerves of adult rats and produced ribonucleotide probes accordingly to track signs of 6-sulphated chondroitins at the site of injury. We found C6st1 mRNA expression in Schwann cells emigrating from explants of both sciatic nerve segments and embryonic dorsal root ganglia. Immunocytochemistry indicated pericellular 6-sulphated chondroitin products around C6ST-1-expressing frontier cells. Motility analysis of frontier cells in cultures subjected to staged treatment with chondroitinase ABC indicated that freshly produced 6-sulphated chondroitin moieties facilitated Schwann cell motility, unlike restrictions resulting from proteoglycan interaction with matrix components. Sciatic nerve crush provided further evidence of in vivo upregulation of the C6ST-1 gene in mobile Schwann cells that guided axonal regrowth 1-14 days post crush; downregulation then accompanied declining mobility of Schwann cells as they engaged in the myelination of re-growing axons. These findings are the first to identify upregulated C6st1 gene expression correlating with the motility of Schwann cells that guide growing axons through both developmental and injured environments.

Animals↗
PubMed2000

Are hyaluronan receptors involved in three-dimensional cell migration?

Hyaluronan (HA), an unbranched polysaccharide consisting of repeated glucuronic acid/N-acetylglucosamine disaccharide units, is ubiquitously present in the extracellular matrix of many tissues (for a more comprehensive review see: Fraser et al., 1997). Increased amounts of hyaluronan are produced by solid tumors and tumor-associated fibroblasts, and tumor-induced HA is correlated with poor prognosis. HA is well known to stimulate the migration of a large variety of cell types. Stimulation of cell migration by HA has been explained by different mechanisms. HA was shown to specifically bind to cell surface receptors, and inhibition of HA-receptor function was demonstrated to decrease cell migration and tumor growth. On the other hand, HA as a large hydrophilic molecule is also known to modulate the extracellular packing of collagen and fibrin, leading to increased fiber size and porosity of extracellular substrates. Hence a modified matrix architecture might similarly account for increased locomotion of cells. In this review, we attempted to summarize the available data on HA-induced cell migration, with particular emphasis on the role of HA receptors in three-dimensional cell migration. Although the HA receptor CD44 has been shown to mediate migration of cells over two-dimensional hyaluronan-coated surfaces in vitro, there is only little evidence that HA-binding to CD44 or other HA receptors has major impact on the locomotion of cells through three-dimensional matrices in vivo. We showed recently that the promigratory effect of HA in fibrin gels is largely due to HA-mediated modulation of fibrin polymerization. By increasing the porosity of fibrin gels, HA strongly accelerates cell migration. The porosity of matrices therefore appears as an important and probably underestimated determinant of cell migration and tumor spread.

Animals↗
PubMed1982

The effect of fibrin on endothelial cell migration in vitro.

Endothelial cells are known to migrate and come into contact with fibrin during numerous physiological processes, such as in wound healing and in tumor growth. The present study was initiated to investigate the effect of fibrin on endothelial cell migration in vitro. Endothelial cell migration was assayed by wounding confluent monolayers of bovine aortic endothelial cells with a razor blade and counting the number of cells crossing the wound per unit time. Wound-induced proliferation of endothelial cells was inhibited by mitomycin C-treatment without affecting endothelial cell migration, indicating that in this assay migration could be measured independent of proliferation. Migration of endothelial cells in vitro was inhibited by fibrin in a concentration dependent manner. Endothelial cell migration under fibrin was further reduced by plasminogen depletion of the serum, and fibrin still inhibited the migration of mitomycin C-treated endothelial cells. Kadish et al. (Tissue and Cell, 11, 99, 1979) previously reported that fibrin did not affect EC migration in vitro. The inability to inhibit EC migration with fibrin appears to be due to their assay system which employed agarose, since pre-treating the wounded monolayer with agarose eliminated the inhibition of EC migration by fibrin. The present results indicate that EC migration in vitro can be used as a model system for studying the interaction of fibrin with EC.

Animals↗
PubMed2006

The minimum element of a synthetic peptide required to block prostate tumor cell migration.

Human prostate tumor cell invasion and metastasis are dependent in part on cell adhesion to extracellular matrix proteins and cell migration. We previously identified a synthetic D-amino acid tumor cell adhesion peptide called HYD1 (kikmviswkg) that supported adhesion of tumor cells derived from breast, prostate, ovary and pancreas tissue. Alanine substitution analysis and a peptide deletion strategy were used to determine the minimal element of HYD1 necessary for bioactivity in a prostate cancer cell line called PC3N. Bioactivity was measured by assays of cell adhesion, migration and ERK signaling. The most potent element of HYD1 necessary to support cell adhesion was kmvixw, the block to migration required xkmviswxx and activation of ERK signaling required ikmviswxx. The shortest sequence active in all three assays was iswkg. The HYD1 peptide contains overlapping elements required for adhesion, blocking migration and the activation of ERK signaling. These linear peptide sequences provide the starting point for development of novel compounds to target cancer cell adhesion and migration.

Amino Acid Sequence↗
PubMed2003

Alpha(v)beta3 integrin expression up-regulates cdc2, which modulates cell migration.

The alphavbeta3 integrin has been shown to promote cell migration through activation of intracellular signaling pathways. We describe here a novel pathway that modulates cell migration and that is activated by alphavbeta3 and, as downstream effector, by cdc2 (cdk1). We report that alphavbeta3 expression in LNCaP (beta3-LNCaP) prostate cancer cells causes increased cdc2 mRNA levels as evaluated by gene expression analysis, and increased cdc2 protein and kinase activity levels. We provide three lines of evidence that increased levels of cdc2 contribute to a motile phenotype on integrin ligands in different cell types. First, increased levels of cdc2 correlate with more motile phenotypes of cancer cells. Second, ectopic expression of cdc2 increases cell migration, whereas expression of dominant-negative cdc2 inhibits migration. Third, cdc2 inhibitors reduce cell migration without affecting cell adhesion. We also show that cdc2 increases cell migration via specific association with cyclin B2, and we unravel a novel pathway of cell motility that involves, downstream of cdc2, caldesmon. cdc2 and caldesmon are shown here to localize in membrane ruffles in motile cells. These results show that cdc2 is a downstream effector of the alphavbeta3 integrin, and that it promotes cell migration.

CDC2 Protein Kinase↗
PubMedDate not supplied

In vitro endothelial wound repair. Interaction of cell migration and proliferation.

Most re-endothelialization requires both cell migration and cell proliferation. To study the association between cell migration and the initiation of DNA synthesis in an in vitro wound model, confluent cultures of porcine aortic endothelial cells grown on glass coverslips were scraped to remove half of the monolayer. Treatment with 1 ng/ml of taxol, a microtubule stabilizing drug, for 24 hours resulted in no visible change in F-actin or microtubule organization as assessed by fluorescence and immunofluorescence microscopy. There was, however, a reduction of wound re-endothelialization and an associated reduction in the proportion of cells with centrosomes redistributed toward the wound edge. No significant differences, however, were seen in the labeling indices for the first two rows of cells at the wound edge as revealed by 3H-thymidine autoradiography. Labeling of nuclei in Rows 3 to 8 and in a zone deeper within the monolayer was reduced in treated cultures. The data suggest that endothelial proliferation in cells within an area bordering a wound is dependent on both denudation, which is sufficient to promote maximal proliferation in the two rows adjacent to the wound, and cell migration, which is required for the propagation of proliferation in cells further away from the wound edge.

Alkaloids↗