Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “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 847 records · Page 47Linked to original sources
PubMed2005

alpha-Crystallin localizes to the leading edges of migrating lens epithelial cells.

alpha-crystallin (alphaA and alphaB) is a major lens protein, which belongs to the small heat-shock family of proteins and binds to various cytoskeletal proteins including actin, vimentin and desmin. In this study, we investigated the cellular localization of alphaA and alphaB-crystallins in migrating epithelial cells isolated from porcine lens. Immunofluorescence localization and confocal imaging of alphaB-crystallin in confluent and in migrating subconfluent cell cultures revealed a distinct pattern of subcellular distribution. While alphaB-crystallin localization was predominantly cytoplasmic in confluent cultures, it was strongly localized to the leading edges of cell membrane or the lamellipodia in migrating cells. In accordance with this pattern, we found abundant levels of alphaB-crystallin in membrane fractions compared to cytosolic and nuclear fractions in migrating lens epithelial cells. alphaA-crystallin, which has 60% sequence identity to alphaB-crystallin, also exhibited a distribution profile localizing to the leading edge of the cell membrane in migrating lens epithelial cells. Localization of alphaB-crystallin to the lamellipodia appears to be dependent on phosphorylation of residue serine-59. An inhibitor of p38 MAP kinase (SB202190), but not the ERK kinase inhibitor PD98059, was found to diminish localization of alphaB-crystallin to the lamellipodia, and this effect was found to be associated with reduced levels of Serine-59 phosphorylated alphaB-crystallin in SB202190-treated migrating lens epithelial cells. alphaB-crystallin localization to the lamellipodia was also altered by the treatment with RGD (Arg-Ala-Asp) peptide, dominant negative N17 Rac1 GTPase, cytochalasin D and Src kinase inhibitor (PP2), but not by the Rho kinase inhibitor Y-27632 or the myosin II inhibitor, blebbistatin. Additionally, in migrating lens epithelial cells, alphaB-crystallin exhibited a clear co-localization with the actin meshwork, beta-catenin, WAVE-1, a promoter of actin nucleation, Abi-2, a component of WAVE-1 protein complex and Arp3, a protein of the actin nucleation complex, suggesting potential interactions between alphaB-crystallin and regulatory proteins involved in actin dynamics and cell adhesion. This is the first report demonstrating specific localization of alphaA and alphaB-crystallins to the lamellipodia in migrating lens epithelial cells and our findings indicate a potential role for alpha-crystallin in actin dynamics during cell migration.

Actin-Related Protein 3↗
PubMed2005

Nested collagen matrices: a new model to study migration of human fibroblast populations in three dimensions.

Fibroblast-3D collagen matrix culture provides a model system to analyze cell physiology under conditions that more closely resemble tissue than conventional 2D cell culture. Previous work has focused primarily on remodeling and contraction of collagen matrices by fibroblasts, and there has been little research on migration of cell populations within the matrix. Here, we introduce a nested collagen matrix model to analyze migration of fibroblasts in 3D collagen matrices. Nested collagen matrices were prepared by embedding contracted cell-containing matrices (also called dermal equivalents) inside cell-free matrices; migration occurred from the former to the latter. Control experiments with human dermal fragments in place of dermal equivalents confirmed the reliability of the model. Human fibroblast migration in nested collagen matrices occurred after a lag phase of 8-16 h, and cells migrating out of the inner matrices were bipolar with leading dendritic extensions. Migration was myosin II, Rho kinase and metalloproteinase-dependent but did not require plasma fibronectin. Platelet-derived growth factor but not lysophosphatidic acid or serum stimulated cell migration, although all three of these physiological agonists promote matrix remodeling and contraction. The nested collagen matrix model is a relatively easy, rapid and quantitative method to measure migration of cell populations. Our studies using this model demonstrate important differences between regulation of fibroblast migration and remodeling in collagen matrices.

Cell Movement↗
PubMed2004

Reactive oxygen species-sensitive p38 MAPK controls thrombin-induced migration of vascular smooth muscle cells.

Thrombin has been implicated in the development of atherosclerosis and restenosis, in which migration of vascular smooth muscle cells (VSMC) is a crucial event. Thrombin-stimulated VSMC migration is associated with increased generation of reactive oxygen species (ROS), activation of mitogen-activated protein kinases (MAPKs), and production of growth factors and chemoattractants. In this study, we examined the interrelation of these signals to determine the pathway controlling thrombin-directed migration of human VSMC. Our results show that thrombin stimulated the production of ROS and activation of p38 MAPK. ROS were required for thrombin-induced VSMC migration since both generation of ROS and cell migration were significantly attenuated by inhibitors of NAD(P)H oxidase, diphenyleneiodonium (DPI) and apocynin (Apo.), and by the hydrogen peroxide scavenger, catalase (Cat.). Activation of p38 MAPK by thrombin was inhibited by DPI, Apo. and Cat., indicating ROS are used as messengers for activating this kinase. p38 MAPK is an important step since SB 203580, a selective inhibitor of p38 MAPK, suppressed the cell migration induced by thrombin. Furthermore, thrombin increased the expression of vascular endothelial growth factor (VEGF), a chemoattractant for VSMC, and this expression was inhibited by DPI, Apo., Cat. and SB 203580. Addition of anti-VEGF antibody significantly attenuated thrombin-induced migration. Collectively, the data presented here show that thrombin has stimulated VSMC migration and VEGF expression through an ROS-sensitive p38 MAPK pathway. VEGF synthesized and released by the cell served as a secondary mediator in thrombin-directed migration.

Cell Movement↗
PubMed2000

Inhibition of vascular smooth muscle cell adhesion and migration by c7E3 Fab (abciximab): a possible mechanism for influencing restenosis.

OBJECTIVES: Brief intravenous administration of chimeric antibody c7E3 Fab during coronary angioplasty has been shown in some studies to provide long term protection against coronary events. Smooth muscle cell (SMC) adhesion and migration are key initial steps in the development of restenosis. The purpose of this study was to investigate the effect of c7E3 Fab on adhesion and migration of SMC to the extracellular matrix (ECM) proteins osteopontin (Opn) and vitronectin (Vn). METHODS: Adhesion of human vascular SMCs to ECM proteins was quantified using a CyQUANT assay kit. Migration of SMCs to Vn, Opn and PDGF was studied using a modified Boyden's chamber migration assay. Integrin expression was determined by immunoprecipitation. RESULTS: c7E3 Fab reduced SMC adhesion on Vn and Opn to 69.2+/-3.3% (P<0.001) and 52.5+/-4.8% (P<0.001) respectively, compared to adhesion without antibody present. This reduction was the same as that for anti-alpha(v)beta(3) integrin antibody LM609 (P=0.5). The combination of anti-alpha(v)beta(5) integrin antibody and c7E3 Fab had a greater effect than either antibody alone (P<0.001). c7E3 Fab reduced SMC migration to Vn and Opn to 51.6+/-8.9% (P<0.001) and 20.3+/-6.1% (P<0.001) respectively, compared to migration in the absence of antibodies. Again, similar results were seen with LM609. PDGF-induced SMC migration was also inhibited by c7E3 Fab (P=0.004) and LM609 (P=0.001), but to much less an extent. The migration SMCs from a culture found not to express the alpha(v)beta(3) integrin was unaffected by these antibodies, strengthening the argument that c7E3 Fab inhibits SMC function via this integrin. CONCLUSIONS: c7E3 Fab inhibits the adhesion and migration of SMCs via the alpha(v)beta(3) integrin. The inhibition, however, is partial, and varied depending on type of ECM protein and alpha(v)beta(3) integrin expression. Some of the clinical benefits of c7E3 Fab may be due to its effect on SMCs.

Abciximab↗
PubMed1995

Heterogeneity in migration of smooth muscle cells from normal and injured rat thoracic aorta in primary culture.

OBJECTIVE: Aside from proliferation, migration of smooth muscle cells is an essential component of the arterial sclerotic reaction. The aim of this study was to define a model to study migration. METHODS: Primary cultures of smooth muscle cells were derived from normal or injured rat thoracic aorta. An image analysis system was used to track cells migrating out of the explants and measure the displacement of their centre of gravity. RESULTS: Migration speeds for smooth muscle cells randomly sampled from the normal whole media were very heterogeneous. The media were therefore separated into three vertical segments. Cells from the middle third migrated faster than those from the upper and lower thirds, regardless of whether they originated from the anterior and posterior parts of the segment (P = 0.001). Heparin (10 micrograms.ml-1) only inhibited smooth muscle cell migration from the middle segment (P < 0.001). Migration of smooth muscle cells from explants of aorta 3 and 14 d after injury was also studied using a balloon catheter. Three days after injury, cell velocity varied widely among the segments of the same media. In contrast, 14 d after injury cells from neointimal explants migrated homogeneously and at a slower rate than those obtained from normal media. CONCLUSIONS: These experiments show migratory variations among smooth muscle cells depending upon their position in the normal aorta and their state of activation after arterial injury. This variability must be taken into account when planning experiments to study smooth muscle cell migration.

Animals↗
PubMed2003

Insulin-like growth factor I-stimulated melanoma cell migration requires phosphoinositide 3-kinase but not extracellular-regulated kinase activation.

Dysregulated signaling contributes to altered cellular growth, motility, and survival during cancer progression. We have evaluated the ability of several factors to stimulate migration in WM1341D, a cell line derived from an invasive human vertical growth phase melanoma. Basic fibroblast growth factor, hepatocyte growth factor, interleukin-8, and CCL27 each slightly increased migration. Insulin-like growth factor I (IGF-I), however, stimulated a 15-fold increase in migration. This response required the IGF-I receptor, which activates phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways. Both pathways have been implicated in migration in a variety of cell types, but the signaling required for IGF-I-induced melanoma cell migration is not well defined. IGF-I-stimulated activation of MAPK/ERK signaling in WM1341D cells was inhibited by U0126, but a 33-fold higher dose of U0126 was needed to inhibit IGF-I-stimulated cellular migration. In contrast, similar concentrations of either wortmannin or LY294002 were required to inhibit both IGF-I-induced PI3K activation and migration. These results indicate that IGF-I-stimulated migration of WM1341D cells requires PI3K activation but is independent of MAPK/ERK signaling. Determining the contributions of IGF-I signaling pathways to migration will help us to understand melanoma progression and may lead to new therapeutic targets of this highly metastatic cancer.

Animals↗
PubMed2003

Regulation of migration of primary prostate epithelial cells by secreted factors from prostate stromal cells.

Stromal-epithelial interactions, which regulate the migration of prostate epithelial cells, play an important role in prostate development, prostatic hyperplasia, and prostate cancer. The objective of this study was to determine how the prostate stroma stimulates the migration of primary prostate epithelial cells (PECs). In the Boyden chamber assay, PEC migration was strongly induced by the conditioned medium of primary prostate stromal cells (PSC-CM). Stimulation of PEC migration depended on the concerted action of adhesion and motility factors in the PSC-CM. Immobilized proteins from PSC-CM mediated adhesion, spreading, and head-to-tail polarization of PECs. Migration induced by immobilized PSC-CM proteins was significantly increased by hepatocyte growth factor/scatter factor (HGF/SF). Inhibition of P13-kinase or Src-family kinases, but not MEK or PLCchi, abolished migration in the Boyden chamber assay. Consistent with their concerted activity in migration assays, the combination of adhesion and motility factors was required for efficient activation of the P13-kinase/Akt pathway. HGF/SF in the PSC-CM was the principal stimulator of the P13-kinase/Akt pathway and an important mediator of PSC-CM-induced PEC migration. In conclusion, our data show that the migration of primary PECs is regulated by the P13-kinase and Src-family kinase signaling pathways and that the activation of the P13-kinase pathway requires adhesion and motility factors from the prostate stroma.

Animals↗
PubMed2003

Role of prostaglandin E2 receptors in migration of murine and human breast cancer cells.

Aberrant upregulation of COX-2 enzyme resulting in accumulation of PGE2 in a cancer cell environment is a marker for progression of many cancers, including breast cancer. Four subtypes of cell surface receptors (EP1, EP2, EP3, and EP4), which are coupled with different G-proteins, mediate PGE2 actions. Since migration is an essential step in invasion and metastasis, in the present study we defined the expression of EP receptors and their roles in migratory function of breast cancer cells of murine (C3L5) and human (MDA-MB-231 and MCF-7) origin. Highly metastatic C3L5 and MDA-MB-231 cells, found to be highly migratory in a Transwell migration assay, were shown to accumulate much higher levels of PGE2 in culture media in comparison with nonmetastatic and poorly migrating MCF-7 cells; the levels of PGF2alpha and 6-keto-PGF1alpha were low in all cases. The elevated PGE2 production by metastatic cancer cells was due to COX-2 activity since dual COX-1/2 inhibitor indomethacin and selective COX-2 inhibitor NS-398 equally suppressed both basal and inducible (by IFN-gamma/LPS or Ca2+-ionophores) PGE2 accumulation. RT-PCR analysis revealed that murine C3L5 cells expressed mRNA of EP1, EP3, and EP4 but not EP2 receptors. On the other hand, human MDA-MB-231 and MCF-7 cells expressed all the above receptors. High levels of expression of functional EP4 receptors coupled with Gs-protein was confirmed in C3L5 cells by biochemical assay showing a dose-dependent increase of intracellular cAMP synthesis in response to PGE2. EP receptor antagonists SC-19220, AH-6809, and AH-23848B, having highest affinity for EP1, EP1/EP2/DP, and EP4 receptors, respectively, variably inhibited migration of metastatic breast cancer cells. An autocrine PGE2-mediated migratory activity of these cells appeared to be associated predominantly with EP4 receptor-mediated signaling pathway, which uses cAMP as a second messenger. This conclusion is based on several observations: (1) selective EP4 antagonist AH-23848B effectively inhibited migration of both C3L5 and MDA-MB-231 cells in a dose-dependent manner; (2) exogenous PGE2 and EP4 agonist PGE1 alcohol increased migration of C3L5 cells; (3) forskolin, a potent activator of adenylate cyclase, as well as membrane-permeable analogues of cAMP (8-bromo-cAMP, dibutyryl-cAMP) stimulated migration of C3L5 cells; and (4) Rp-cAMPS, a selective protein kinase A inhibitor, reduced migration of C3L5 cells. Migration of poorly migratory MCF-7 cells remained unaffected with either PGE2 or EP4 antagonist. These findings are relevant for designing therapeutic strategies against breast cancer metastasis.

Alprostadil↗
PubMed1996

Mononuclear cell conditioned medium enhances bronchial epithelial cell migration but inhibits attachment to fibronectin.

The attachment and migration of bronchial epithelial cells are important features in re-epithelialization after tissue injury. We hypothesized that inflammatory cytokines might alter bronchial epithelial cell attachment and migration. To test this hypothesis, we evaluated the effects of mononuclear cell conditioned medium (MNCCM) on attachment and migration of bronchial epithelial cells to fibronectin in vitro. MNCCM was prepared from bovine blood mononuclear cells that were stimulated with concanavalin A. MNCCM stimulated bronchial epithelial cell migration and spreading. Sephadex G-75 column chromatography of MNCCM found two peaks of migration-stimulatory activity. Activity in the higher molecular weight peak was partially inhibited by anti-tumor necrosis factor-alpha antibodies. Activity in the low-molecular-weight peak was lipid-extractable, suggesting the possibility that the activity was an arachidonate metabolite. We evaluated the effects of protein kinase C (PKC) inhibitors on enhancement of bronchial epithelial cell migration by MNCCM under the hypothesis that stimulated bronchial epithelial cell migration by MNCCM was elicited through PKC-dependent signaling pathways. PKC inhibitors, calphostin and H-7, inhibited the effect of MNCCM on bronchial epithelial cell migration. In addition, MNCCM stimulated PKC translocation and activity in these cells. Thus mononuclear cells produce inflammatory cytokines with important effects on bronchial epithelial cell migration and spreading. The stimulatory effect may be mediated in part through PKC signaling pathways.

Actins↗
PubMed2003

Cyclic AMP inhibits production of interleukin-6 and migration in human vascular smooth muscle cells.

BACKGROUND: Gene expression induced by tumor necrosis factor-alpha (TNF-alpha) is involved in the regulation of vascular smooth muscle cell (VSMC) proliferation and migration, two events critical to formation of stenotic vascular lesions. In some systems, elevating adenosine 3',5'-cyclic monophosphate (cyclic AMP) inhibits TNF-alpha induced gene transcription. We recently demonstrated that interleukin-6 (IL-6) was chemotactic to VSMC. Therefore, we tested the hypothesis that elevating cyclic AMP would inhibit TNF-alpha-mediated IL-6 expression and VSMC migration. MATERIALS AND METHODS: VSMC were cultured from saphenous vein remaining after coronary artery bypass grafting. Migration of VSMC through a porous membrane was determined. Intracellular cyclic AMP was elevated by exposing the cells to forskolin or 8-Br-cyclic AMP and was measured by radioimmunoassay. IL-6 was measured by enzyme-linked immunosorbent assay. RESULTS: TNF-alpha induced migration of VSMC in a concentration-dependent manner. Incubation of cells with forskolin significantly increased cyclic AMP. Co-incubation of cells with TNF-alpha in combination with 8-Br-cyclic AMP or forskolin inhibited migration by approximately 25 and 70%, respectively. Incubation with TNF-alpha increased release of IL-6 from VSMC 18-fold over basal. This stimulated release was inhibited by either 8-Br-cyclic AMP or forskolin. In cells stimulated with TNF-alpha, addition of an antibody to IL-6 reduced migration by 25%. CONCLUSIONS: These data show that IL-6 produced by VSMC contributes to cell migration induced by TNF-alpha. Further, elevating cyclic AMP inhibited TNF-alpha-induced release of IL-6, and migration of VSMC. These results are consistent with the notion that mechanisms that increase intracellular cyclic AMP, such as activation of beta-adrenergic receptors on VSMC, act as a brake on cell migration.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2003

Adhesion and migration of extracellular matrix-stimulated breast cancer.

BACKGROUND: Extracellular matrix (ECM) components, such as vitronectin and fibronectin, have been shown to enhance the metastatic potential of breast cancer cells. We hypothesized that ECM binding to integrin receptors on breast cancer cells influenced cellular adhesion and migration. MATERIALS AND METHODS: Adhesion assays were performed using breast cancer cell lines MDA-MB-435 and MDA-MB-231 and various concentrations of vitronectin or fibronectin. Migration assays were performed using the same cell lines and invasion chambers with 8 microm pore polycarbonate membranes. Blocking antibodies and specific peptidomimetic inhibitors to integrin receptors were used to identify the integrin subunits reacting with vitronectin and fibronectin. RESULTS: While both breast cancer cell lines adhered to and migrated toward vitronectin and fibronectin, MDA-MB-435 had a higher maximum binding to vitronectin and MDA-MB-231 had a higher maximum binding to fibronectin. Anti-beta1 antibody inhibited the adhesion and migration of MDA-MB-231 to fibronectin and the adhesion of MDA-MB-231 to vitronectin but had no effect on vitronectin-induced adhesion or migration of MDA-MB-435. The alpha(v)beta3/alpha(v)beta5 antagonist, SB 265123, inhibited MDA-MB-231 and MDA-MB-435 adhesion and migration to vitronectin but had no effect on migration to fibronectin in either cell line. CONCLUSIONS: We conclude that the integrin subunits beta1, alpha(v)beta3, and alpha(v)beta5 can be involved in breast cancer cell adhesion and migration to vitronectin and fibronectin. Because more than one integrin inhibitor was required to block adhesion or migration in the cell lines studied, breast cancer therapy based on integrin antagonists would most likely require concomitant use of multiple agents.

Acetates↗
PubMed2002

Comparison of gene expression patterns and migration capability at quiescent and proliferating vascular smooth muscle cells stimulated by cytokines.

The changes of the gene expression patterns and the migration capability of vascular smooth muscle cells (VSMC) at the quiescent and proliferating states were investigated after VSMC was stimulated by cytokines. VSMC migration was measured using a model of wounding injury of confluent cultured cells and a Boyden chamber assay. The migration distance of the quiescent VSMC induced by cytokines bFGF, IL-1beta and TNF-alpha was 5.8, 4.7, and 4.2 times as long as that of the control group, respectively. However, the migration distance of the proliferating VSMC was only one-fourth of the quiescent cells under the same effects. The results of Boyden chamber assay indicated that VSMC was capable of degrading collagen and traversed the pores of membrane barriers in response to bFGF as a chemoattractant, and VSMC number across the membrane was markedly increased as concentration gradient of bFGF ascended. Northern blot and nuclear run-off assay showed that bFGF not only stimulated the expression of migration-related matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) but also enhanced the transcription of proliferation-related osteopontin (OPN) and c-jun genes in the quiescent VSMC. bFGF could moderately increase the expression of OPN and c-jun, but had no significant effect on the expression of MMP-2 and TIMP-2 in the proliferating cells under the same conditions. These findings suggest that VSMC migration capability and the expression activity of migration- and proliferation-related genes were significantly distinct for the quiescent and proliferating VSMC. The cellular migration capability and the expression activity of migration-related genes in the quiescent VSMC were much higher than those in the proliferating cells in response to cytokines.

Animals↗
PubMed1999

Substrate-adsorbed collagen and cell secreted fibronectin concertedly induce cell migration on poly(lactide-glycolide) substrates.

Limited epithelial cell migration on synthetic polymeric biomaterials, such as polyesters, presents a serious challenge to their use as scaffolds for artificial skin analogs. The mechanisms by which a physiologic matrix interface on such polymers may regulate and promote cell migration under 'activated conditions' were the focus of this study. We have quantified the migration behavior of epidermal growth factor (EGF) stimulated epidermal keratinocytes on 50:50 poly-D,L(lactide-glycolide) (PLGA) substrates, following exogenous and cell-derived substrate conditioning based on the model matrix proteins, collagen and fibronectin. We report that 'non-conditioned' PLGA substrates elicited poor levels of keratinocyte migration. However, keratinocyte migration was significantly enhanced upon the adsorption of type I collagen, and was only weakly enhanced with fibronectin adsorption. Molecular analysis of the mechanism of enhanced migration on collagen-PLGA substrates showed that keratinocyte migration was sensitive to cell-derived fibronectin conditioning, but not to cell-secreted collagen conditioning. Fibronectin control of cell migration on collagen-PLGA was found to be both stoichiometric and biologically specific, mediated via adhesion involving keratinocyte alpha v integrin receptors. Based on our results, we propose a unique paradigm for induction of cell migration on a non-physiologic synthetic polymer using concerted interactions between primary, polymer-instructed matrix remodeling and secondary, cell-derived matrix remodeling.

Adsorption↗
PubMed2000

Mechanism of calcium oscillations in migrating human astrocytoma cells.

Numerous studies show that intracellular calcium controls the migration rate of different mobile cell types. We studied migrating astrocytoma cells from two human cell lines, U-87MG and A172, in order to clarify the mechanisms by which calcium potentially influences cell migration. Using the wound-healing model to assay migration, we showed that four distinct components of migration could be distinguished: (i) a Ca(2+)/serum-dependent process; (ii) a Ca(2+)-dependent/serum-independent process; (iii) a Ca(2+)/serum-independent process; (iv) a Ca(2+)-independent/serum-dependent process. In U-87MG cells which lack a Ca(2+)-dependent/serum-independent component, we found that intracellular Ca(2+) oscillations are involved in Ca(2+)-dependent migration. Removing extracellular Ca(2+) greatly decreased the frequency of migration-associated Ca(2+) oscillations. Furthermore, non-selective inhibition of Ca(2+) channels by heavy metals such as Cd(2+) or La(3+) almost completely abolished changes in intracellular Ca(2+) observed during migration, indicating an essential role for Ca(2+) channels in the generation of these Ca(2+) oscillations. However, specific blockers of voltage-gated Ca(2+) channels, including nitrendipine, omega-conotoxin GVIA, omega-conotoxin MVIIC or low concentrations of Ni(2+) were without effect on Ca(2+) oscillations. We examined the role of internal Ca(2+) stores, showing that thapsigargin-sensitive Ca(2+) stores and InsP(3) receptors are involved in Ca(2+) oscillations, unlike ryanodine-sensitive Ca(2+) stores. Detailed analysis of the spatio-temporal aspect of the Ca(2+) oscillations revealed the existence of Ca(2+) waves initiated at the leading cell edge which propagate throughout the cell. Previously, we have shown that the frequency of Ca(2+) oscillations was reduced in the presence of inhibitory antibodies directed against beta3 integrin subunits. A simple model of a Ca(2+) oscillator is proposed, which may explain how the generation of Ca(2+) oscillations is linked to cell migration.

Astrocytoma↗
PubMed2004

Alpha-tocopherol preserves endothelial cell migration in the presence of cell-oxidized low-density lipoprotein by inhibiting changes in cell membrane fluidity.

OBJECTIVE: Endothelial cell (EC) migration is essential for healing areas of arterial injury and angioplasty sites. Iron or copper-oxidized low-density lipoprotein (oxLDL(Cu)) inhibits EC migration in vitro, but the effect of physiologically relevant monocyte/macrophage-oxidized LDL (oxLDL(cell)) is unknown. We postulated that oxLDL(cell) would inhibit EC migration and that this inhibition would be reversed by antioxidants. METHODS: The effect of oxLDL(Cu) and oxLDL(cell) on EC migration was studied by using a razor scrape assay, and migration was assessed after 24 hours. In addition, ECs were incubated with various antioxidants, including butylated hydroxytoluene (BHT), probucol, or alpha-tocopherol, for 1 hour prior to initiation of the scrape assay and application of oxLDL. RESULTS: Both oxLDL(Cu) and oxLDL(cell) inhibited migration. The antioxidants did not alter the antimigratory activity of oxLDL(Cu), but alpha-tocopherol preserved EC migration in the presence of oxLDL(cell). The lack of effect of BHT or probucol suggested that the effect of alpha-tocopherol resided not in its antioxidant activity but in its membrane-stabilizing properties. To test this theory, the effect of oxLDL and alpha-tocopherol on relative cell membrane fluidity was assessed by fluorescence recovery after photobleaching. Both oxLDL(Cu) and oxLDL(cell) increased relative membrane fluidity. Preincubation with alpha-tocopherol inhibited the increase in membrane fluidity of ECs incubated in oxLDL(cell) but not in oxLDL(Cu). CONCLUSIONS: These studies show that alpha-tocopherol preserves EC migration in oxLDL(cell) and hastens restoration of the endothelial monolayer after injury by inhibiting changes in membrane integrity caused by oxLDL. CLINICAL RELEVANCE: Recent studies find that vitamin E is not efficacious in the secondary prevention of cardiovascular events, perhaps because vitamin E does not efficiently block oxidation pathways known to be operative in atherosclerotic arteries. "Non-antioxidant" properties of vitamin E, however, could be important in the primary prevention of atherosclerosis and its complications. Our in vitro studies show that alpha-tocopherol can preserve endothelial migration in the presence of cell-oxidized LDL. This effect might improve the healing of endothelial injuries at sites of arterial repair or angioplasties, especially in lipid-laden arterial walls.

Animals↗
PubMed2003

Effect of tenascin and fibronectin on the migration of human corneal fibroblasts.

PURPOSE: To investigate the effect of fibronectin and tenascin on the migration of corneal fibroblasts. SETTING: Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria. METHODS: Using human corneal fibroblasts, a monolayer migration assay was performed to measure corneal fibroblast movement. The migration on collagen I, fibronectin, and tenascin with and without transforming growth factor (TGF)-alpha/fibroblast growth factor (FGF)-2 stimulation and the effect of soluble tenascin and fibronectin on corneal fibroblast migration on collagen-I-coated wells were investigated. RESULTS: The cytokines TGF-alpha and FGF-2 stimulated migrational activity of corneal stromal cells in a dose-dependent manner, reaching the maximum effect at 100 ng/mL and 10 ng/mL, respectively. The migration of corneal fibroblasts on fibronectin was significantly higher (P <.05) than the migration on collagen I. Transforming growth factor-alpha and FGF-2 increased radial cell displacement independent of the provided matrix composition. Tenascin had a negative effect on corneal fibroblast adhesion/migration in this in vitro model. CONCLUSION: Fibronectin and tenascin influenced corneal fibroblast migration and adhesion, respectively, and may play a role in stromal cell movement during wound healing. The cytokines TGF-alpha and FGF-2 had an additive effect on corneal fibroblast migration on a fibronectin matrix.

Cell Adhesion↗
PubMed1998

vab-8 is a key regulator of posteriorly directed migrations in C. elegans and encodes a novel protein with kinesin motor similarity.

Nervous system assembly requires the directed migrations of cells and axon growth cones along the dorsoventral and anteroposterior axes. Although guidance mechanisms for dorsoventral migrations are conserved from nematodes to mammals, mechanisms for anteroposterior migrations are unknown. In C. elegans, the gene vab-8, which specifically functions in posteriorly directed migrations, encodes two isoforms of a novel intracellular protein that act cell-autonomously in different migrations. VAB-8L, which contains a domain similar to kinesin-like motors, functions in all vab-8-dependent axon growth cone migrations. VAB-8S, which lacks this N-terminal domain, functions in a subset of vab-8-dependent cell migrations. Continuous expression of VAB-8L in the ALM mechanosensory neuron, which normally requires vab-8 early in its development for posteriorly directed cell migration, redirects its anteriorly projecting axon posteriorly. We propose that regulation of vab-8 activity is a mechanism for controlling the direction of cell and axon growth cone migrations.

Amino Acid Sequence↗
PubMed2000

The physiological state of captive and migrating Great White Pelicans (Pelecanus onocrotalus) revealed by their blood chemistry.

The Great White Pelican Pelecanus onocrotalus is an endangered migratory bird, threatened by diminishing natural feeding sites and by persecution by fishermen. The majority of the migrating White Pelican (71000) stop-over in Israel during their autumn migration to Africa. As part of a larger study, aimed to assess the necessity of feeding during the stop-over in Israel, we examined the blood chemistry of captive and migrating White Pelicans. Blood was sampled from captive birds maintained on a fish diet, after food deprivation for 48 h and from wild birds brought from the field during migration. Food deprivation resulted in increased plasma levels of triglycerides and in lower levels of urea, potassium and calcium. In migrating birds, increased plasma levels of urea and CPK and lower levels of creatinine were revealed. In general, the coefficient of variation in the blood chemistry of migrating pelicans was higher than in the captive birds, that is to say, that these birds were in a variable physiological condition. The blood profile of migrating and wintering pelicans did not indicate a state of dehydration but did indicate energy deficiency. The less extreme changes in blood chemistry of the 48 h food-deprived compared to migrating pelicans suggest that the former did not reach a state of starvation. We conclude that for White Pelicans the stop-over in Israel is a must in order to rest and replenish their fuel reserves for completion of their autumn migration to Africa.

Animals↗