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At least 145 records · Page 8Linked to original sources
PubMed2004

Two distinct actin networks drive the protrusion of migrating cells.

Cell migration initiates by extension of the actin cytoskeleton at the leading edge. Computational analysis of fluorescent speckle microscopy movies of migrating epithelial cells revealed this process is mediated by two spatially colocalized but kinematically, kinetically, molecularly, and functionally distinct actin networks. A lamellipodium network assembled at the leading edge but completely disassembled within 1 to 3 micrometers. It was weakly coupled to the rest of the cytoskeleton and promoted the random protrusion and retraction of the leading edge. Productive cell advance was a function of the second colocalized network, the lamella, where actomyosin contraction was integrated with substrate adhesion.

Actin Cytoskeleton↗
PubMed1990

Spatial and temporal patterns of interstitial cell migration in Hydra vulgaris.

Interstitial cell migration was characterized in Hydra vulgaris (formerly H. attenuata) and the effects of axial position and tissue injury on migration were investigated. Migrating cells were labeled with the thymidine analog, bromodeoxyuridine, and grafted into unlabeled host polyps. Alternatively, cells were labeled directly in hosts with the fluorescent, carbocyanine dye, DiI. The results show that cell migration appeared constrained to proximal (toward the basal disk) or distal (toward the tentacles) movements, but were never lateral. Some cells moved bidirectionally. The fastest migrating cells moved an average of 28 microns/hr. Two to six percent of the gastric region interstitial cells migrated in 1 day and accumulated throughout the body column. In grafted polyps, an average of eight cells emigrated from midgastric regions every hour. Tissue injury had no observed effect on the amount of cell migration. Cells emigrating from midgastric regions showed a preference for distal accumulation, and this bias was enhanced when migrating cells originated from more distal positions in the polyp. Proximally derived tissue grafted to a more distal position also showed similar, preferential distal migration, indicating that interstitial cell migration patterns are dependent upon their position in the body column and not upon their origin. Migrating interstitial cells are slower moving and less numerous than migrating nematocytes in H. vulgaris, but since their migration patterns are similar, the migration of both cell types may be influenced by the same directional cues.

Animals↗
PubMed2003

NOVH increases MMP3 expression and cell migration in glioblastoma cells via a PDGFR-alpha-dependent mechanism.

Nephroblastoma overexpressed gene (NOV) is highly expressed in the nervous system. We investigated its biological activity by expressing the human NOV gene (NOVH) in a human glioblastoma cell line that is negative for NOVH and by analyzing four clones with different levels of NOVH expression. There was no difference in cell proliferation between the NOVH-expressing cell lines, but there was increased cell adhesion and migration that correlated with increasing NOVH expression. Gene expression profiling was used to investigate the mechanisms by which NOVH expression regulated cell activity. We identified two induced genes in NOVH-expressing cells that are involved in cell migration: matrix metalloprotease (MMP)3 and platelet-derived growth factor receptor (PDGFR)-alpha. Our studies show that PDGFR-alpha induced MMP3 gene expression and increased cell proliferation and cell migration upon stimulation by platelet-derived growth factor (PDGF)-AA. We also show that the induction of MMP3 in cells expressing NOVH is potentiated by either cell density, serum, or PDGF-BB. Thus, expression of NOVH in glioblastoma cells triggers a cascade of gene expression resulting in increased cell adhesion and migration.

Becaplermin↗
PubMed2006

Syk tyrosine kinase mediates Epstein-Barr virus latent membrane protein 2A-induced cell migration in epithelial cells.

Although spleen tyrosine kinase (Syk) is known to be important in hematopoietic cell development, the roles of Syk in epithelial cells have not been well studied. Limited data suggest that Syk plays alternate roles in carcinogenesis under different circumstances. In breast cancer, Syk has been suggested to be a tumor suppressor. In contrast, Syk is essential for murine mammary tumor virus-mediated transformation. However, the roles of Syk in tumor migration are still largely unknown. Nasopharyngeal carcinoma, an unusually highly metastatic tumor, expresses Epstein-Barr virus LMP2A (latent membrane protein 2A) in most clinical specimens. Previously, we demonstrated LMP2A triggers epithelial cell migration. LMP2A contains an immunoreceptor tyrosine-based activation motif, which is important for Syk kinase activation in B cells. In this study, we explored whether Syk is important for LMP2A-mediated epithelial cell migration. We demonstrate that LMP2A expression can activate endogenous Syk activity. The activation requires the tyrosine residues in LMP2A ITAM but not YEEA motif, which is important for Syk activation by Lyn in B cells. LMP2A interacts with Syk as demonstrated by coimmunoprecipitation and confocal microscopy. Furthermore, LMP2A-induced cell migration is inhibited by a Syk inhibitor and short interfering RNA. Tyrosines 74 and 85 in the LMP2A immunoreceptor tyrosine-based activation motif are essential for both Syk activation and LMP2A-mediated cell migration, indicating the involvement of Syk in LMP2A-triggered cell migration. The LMP2A-Syk pathway may provide suitable drug targets for treatment of nasopharyngeal carcinoma.

Amino Acid Sequence↗
PubMed2003

TGF-beta1-promoted epithelial-to-mesenchymal transformation and cell adhesion contribute to TGF-beta1-enhanced cell migration in SMMC-7721 cells.

Transforming growth factor-b1 (TGF-beta1), a multi-function polypeptide, is a double-edged sword in cancer. For some tumor cells, TGF-beta1 is a potent growth inhibitor and apoptosis inducer. More commonly, TGF-beta1 loses its growth-inhibitory and apoptosis-inducing effects, but stimulates the metastatic capacity of tumor cells. It is currently little known about TGF-beta1-promoted cell migration in hepatocellular carcinoma (HCC) cells, let alone its mechanism. In this study, we found that TGF-beta1 lost its tumor-suppressive effects, but significantly stimulated cell migration in SMMC-7721 human HCC cells. By FACS and Western blot analysis, we observed that TGF-beta1 enhanced the expression of alpha5beta1 integrin obviously, and subsequently stimulated cell adhesion onto fibronectin (Fn). Furthermore, we observed that TGF-beta1 could also promote SMMC-7721 cells adhesion onto laminin (Ln). Our data also provided evidences that TGF-beta1 induced epithelial-to-mesenchymal transformation (EMT) in SMMC-7721 cells. First, SMMC-7721 cells clearly switched to the spindle shape morphology after TGF-beta1 treatment. Furthermore, TGF-beta1 induced the down-regulation of E-cadherin and the nuclear translocation of beta-catenin. These results indicated that TGF-beta1-promoted cell adhesion and TGF-beta1-induced epithelial-to-mesenchymal transformation might be both responsible for TGF-beta1-enhanced cell migration.

Carcinoma, Hepatocellular↗
PubMed1984

Interstitial cell migration in Hydra attenuata. II. Selective migration of nerve cell precursors as the basis for position-dependent nerve cell differentiation.

In Hydra, the interstitial cells constitute a multipotent stem cell system, forming nerve cells and nematocytes. Differentiation of these product cells varies in an axially dependent manner along the body column, and either of two simple hypotheses can explain this phenomena: (1) position-dependent stem cell determination or (2) selective migration of committed precursor cells. This latter hypothesis predicts that the migrating interstitial cell population is enriched with cells which are restricted in their proliferation and differentiation potential. To test this idea several developmental properties of the migrating cells were compared with those of the total interstitial cell population. The results indicate that those interstitial cells that migrate are not a random sample of the whole population. They contain a lower proportion of stem cells, as shown both by a slower growth rate and by a reduced capacity for clone formation. The migrating population is specifically enriched with interstitial cells that are committed to nerve differentiation. Coupled with previous measurements on migration rates, these findings suggest that the observed position-dependent pattern of nerve differentiation results from the selective redistribution of committed nerve cell precursors.

Animals↗
PubMed2006

Vacuolar-type H+-ATPases at the plasma membrane regulate pH and cell migration in microvascular endothelial cells.

Microvascular endothelial cells involved in angiogenesis are exposed to an acidic environment that is not conducive for growth and survival. These cells must exhibit a dynamic intracellular (cytosolic) pH (pHcyt) regulatory mechanism to cope with acidosis, in addition to the ubiquitous Na+/H+ exchanger and HCO3--based H+-transporting systems. We hypothesize that the presence of plasmalemmal vacuolar-type proton ATPases (pmV-ATPases) allows microvascular endothelial cells to better cope with this acidic environment and that pmV-ATPases are required for cell migration. This study indicates that microvascular endothelial cells, which are more migratory than macrovascular endothelial cells, express pmV-ATPases. Spectral imaging microscopy indicates a more alkaline pHcyt at the leading than at the lagging edge of microvascular endothelial cells. Treatment of microvascular endothelial cells with V-ATPase inhibitors decreases the proton fluxes via pmV-ATPases and cell migration. These data suggest that pmV-ATPases are essential for pHcyt regulation and cell migration in microvascular endothelial cells.

Animals↗
PubMed2005

Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells.

Cdc42 is a small GTPase involved in the regulation of the cytoskeleton and cell polarity. To test whether Cdc42 has an essential role in the formation of filopodia or directed cell migration, we generated Cdc42-deficient fibroblastoid cells by conditional gene inactivation. We report here that loss of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi apparatus into the direction of migration was decreased. However, expression of dominant negative Cdc42 in Cdc42-null cells resulted in strongly reduced directed migration, severely reduced single cell directionality, and complete loss of Golgi polarization and of directionality of protrusion formation toward the wound, as well as membrane blebbing. Thus, our data show that besides Cdc42 additional GTPases of the Rho-family, which share GEFs with Cdc42, are involved in the establishment and maintenance of cell polarity during directed migration.

Cell Adhesion↗
PubMed2004

Invadolysin: a novel, conserved metalloprotease links mitotic structural rearrangements with cell migration.

The cell cycle is widely known to be regulated by networks of phosphorylation and ubiquitin-directed proteolysis. Here, we describe IX-14/invadolysin, a novel metalloprotease present only in metazoa, whose activity appears to be essential for mitotic progression. Mitotic neuroblasts of Drosophila melanogaster IX-14 mutant larvae exhibit increased levels of nuclear envelope proteins, monopolar and asymmetric spindles, and chromosomes that appear hypercondensed in length with a surrounding halo of loosely condensed chromatin. Zymography reveals that a protease activity, present in wild-type larval brains, is missing from homozygous tissue, and we show that IX-14/invadolysin cleaves lamin in vitro. The IX-14/invadolysin protein is predominantly found in cytoplasmic structures resembling invadopodia in fly and human cells, but is dramatically relocalized to the leading edge of migrating cells. Strikingly, we find that the directed migration of germ cells is affected in Drosophila IX-14 mutant embryos. Thus, invadolysin identifies a new family of conserved metalloproteases whose activity appears to be essential for the coordination of mitotic progression, but which also plays an unexpected role in cell migration.

Animals↗
PubMed2005

Accelerated dendritic-cell migration and T-cell priming in SPARC-deficient mice.

On their path to draining lymph nodes, epidermal Langerhans cells traverse collagen-dense connective tissue before reaching lymphatic vessels. The matricellular protein SPARC (secreted protein, acidic and rich in cysteine), which is induced during inflammation and tissue repair, organizes collagen deposition in tissue stroma. We analyzed Langerhans cell and dendritic-cell migration and its impact on T-cell priming in SPARC-null (SPARC(-/-)) and SPARC-sufficient (SPARC(+/+)) mice. Although the same number of Langerhans cells populate the ear skin of SPARC(-/-) and SPARC(+/+) mice, more Langerhans cells were found in the lymph nodes draining antigen-sensitized ears of SPARC(-/-) mice and significantly more Langerhans cells migrated from null-mice-derived ear skin explants. Such favored Langerhans cell migration is due to the host environment, as demonstrated by SPARC(+/+)>SPARC(-/-) and reciprocal chimeras, and have a profound influence on T-cell priming. Contact-, delayed type-hypersensitivity and naive T-cell receptor-transgenic T-cell priming, together indicate that the lack of SPARC in the environment accelerates the onset of T-cell priming by hastening Langerhans cell/dendritic-cell migration.

Animals↗
PubMed2025

Galvanin (TMEM154) is an electric-field sensor for directed cell migration.

Directed cell migration of immune and epithelial cells is critical for their rapid response to tissue injury or infection. Endogenous electric fields generated by disruption of the transepithelial potential across the skin have been postulated to play an important role in guiding cells to wound sites, though how individual cells sense these tissue-scale physical cues remains largely unknown. We have identified Galvanin (TMEM154), a previously uncharacterized single-pass transmembrane protein, as being required for electric-field-guided migration of individual rapidly moving cells. Galvanin functions in both immune and epithelial cell types. Upon exposure of cells to an electric field, Galvanin rapidly relocalizes to the anodal side of a cell, and the net charge on its extracellular domain is necessary and sufficient to drive this spatial relocalization. Furthermore, expression of Galvanin is sufficient to confer electric field-guided migration on otherwise non-responsive epithelial cells. In human neutrophils, we show that Galvanin relocalization is immediately followed by changes in the spatial pattern of cellular protrusion and retraction. The strong directional response of these cells is lost upon truncation of Galvanin's intracellular domain, suggesting that Galvanin acts as a direct sensor of the electric field, transducing spatial information about a cell's electrical environment to the intracellular migratory apparatus. This sensor relocalization mechanism of cell steering defines a new paradigm for directed cell migration.

Journal Article↗
PubMed2005

5-Fluorouracil interferes with actin organization, stress fiber formation and cell migration in corneal endothelial cells during wound repair along the natural basement membrane.

Corneal endothelial cells respond to a circular freeze wound by undergoing actin cytoskeletal reorganization that is mainly characterized by the disappearance of circumferential microfilament bundles (CMBs) and the subsequent appearance of distinct stress fibers. This cytoskeletal rearrangement is associated with changes in cell shape as migrating cells lose their polyhedral appearance, spread out, and assume a stellate morphology with cell processes extending outward into the injured area. We report here that in the presence of low concentrations (0.01-0.l mM) of the anti-metabolite 5-fluorouracil (5-FU), characteristic actin organization becomes disrupted and migrating cells do not display elongated processes typical of control tissues and translocation into the injury zone is retarded, but not inhibited. Rhodamine phalloidin staining revealed no evidence of stress fiber formation. A higher concentration of 5-FU (1.0 mM) not only prevented formation of discernible stress fibers but also resulted in a more restricted cell movement during wound repair. That this was not a cytotoxic effect was demonstrated by transferring tissues back into standard medium allowing endothelia to reinitiate migration and undergo complete wound healing by 72 h post-transfer. Overnight incubation of endothelia in 4 muM phallacidin resulted in limited CMB disruption the extent of which was dependent on the 5-FU concentration. The effects of 5-FU on the actin cytoskeleton are reversible and by 24 h after placing treated endothelia into medium without 5-FU, actin begins to become re-established and by 48 h microfilament patterns in the tissue resemble those of non-treated endothelia. Similarly, when non-injured tissues are cultured in the presence of 5-FU for 24 h, subsequently injured and returned to standard medium, they exhibit no stress fibers when observed at 24 h post-wounding. However, by 48 h post-injury these cells now display stress fibers and extend processes into the wound area. Biochemical studies on isolated muscle actin demonstrated that actin polymerization is unaffected in the presence of either 0.01 or 1 mM 5-FU as determined by the F-actin sedimentation and falling ball viscosity techniques. Thus, the mechanism(s) by which 5-FU exerts its actions on the actin cytoskeleton appears to be one of an indirect nature.

Actins↗
PubMed1997

Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness.

Migration of cells in higher organisms is mediated by adhesion receptors, such as integrins, that link the cell to extracellular-matrix ligands, transmitting forces and signals necessary for locomotion. Whether cells will migrate or not on a given substratum, and also their speed, depends on several variables related to integrin-ligand interactions, including ligand levels, integrin levels, and integrin-ligand binding affinities. These and other factors affect the way molecular systems integrate to effect and regulate cell migration. Here we show that changes in cell migration speed resulting from three separate variables-substratum ligand level, cell integrin expression level, and integrin-ligand binding affinity-are all quantitatively predictable through the changes they cause in a single unifying parameter: short-term cell-substratum adhesion strength. This finding is consistent with predictions of a mathematical model for cell migration. The ligand concentration promoting maximum migration speed decreases reciprocally as integrin expression increases. Increases in integrin-ligand affinity similarly result in maximal migration at reciprocally lower ligand concentrations. The maximum speed attainable, however, remains unchanged as ligand concentration, integrin expression, or integrin-ligand affinity vary, suggesting that integrin coupling with intracellular motors remains unaltered.

Animals↗
PubMed2005

Association of hnRNP S1 proteins with vimentin intermediate filaments in migrating cells.

S1 proteins C2 and D2 are multifunctional hnRNP proteins acting as transcriptional regulators in the nucleus. Immunofluorescence staining of various cells in culture revealed that S1 proteins also occur in the cytoplasm, often in association with vimentin intermediate filaments (VFs). Here, we verified the association of S1 proteins with vimentin using vimentin-deficient cells, crosslinking and immunoprecipitation, and further investigated the biological significance of this association. S1 proteins on VFs, referred to here as S1 fibers, were lost in highly confluent cells, where cell proliferation and cellular metabolic activity greatly decreased owing to cell density-dependent arrest. However, the disappearance of S1 fibers was not related to these reduced activities, but to inhibited cell migration. Although undetected in cells of non-migratory tissues as well as in confluent cultured cells, S1 fibers were found in all migratory cells examined, such as cultured cells in scratch/wound experiments, blood neutrophils and monocytes, and fibroblasts engaging in tissue healing. In addition, S1 fibers reappeared even in confluent cells when VFs were induced to reorganize with okadaic acid. We propose that S1 proteins occur in association with VFs in migratory cells. Possible participation of S1 proteins in the formation/reorganization of VFs is discussed.

Animals↗
PubMed1997

Fibronectin-mediated cell migration promotes glioma cell invasion through chemokinetic activity.

In order to investigate the biological role of fibronectin in glioma cell invasion, we studied the relation between migratory responses or adhesiveness of glioma cells to fibronectin and the in vitro invasion in three human malignant glioma cell lines, A172, T98G and U373MG. All these cell lines chemotactically migrated in a dose-dependent manner to fibronectin in concentrations ranging from 0.5 to 10 microg/ml, with A172 cells showing the strongest migration and U373 cells the weakest. Checkerboard analyses demonstrated that A172 and T98G cells showed much stronger chemokinetic responses to fibronectin than U373MG cells. In contrast to the migratory responses, A172 and U373MG cells showed an almost equally high adhesion to fibronectin and T98G cells a low adhesion. The degree of expression of the integrin alpha5 subunit correlated well with the strength of glioma cell adhesion to fibronectin rather than that of migration to the molecule. Furthermore, the cell adhesion to fibronectin was almost completely inhibited by arginine-glycine-aspartic acid (RGD)-containing peptides, but the fibronectin-stimulated cell migration was only partially inhibited. An in vitro invasion assay disclosed that U373MG cells invaded the artificial basement membrane barrier the most and A172 cells the least. However, addition of fibronectin to the glioma cells markedly enhanced the invasive activity of A172 and T98G cells but had little effect on that of U373MG cells. These results indicate that fibronectin-stimulated migration can be one of the factors promoting invasiveness of glioma cells and that the chemokinetic activity of fibronectin may play a crucial role in glioma invasion through conferring motor-driving force on the glioma cells.

Cell Adhesion↗
PubMed1995

Cell migration from the olfactory placode and the ontogeny of the neuroendocrine compartments.

The olfactory placode and its derivative, the olfactory pit, give rise to several different populations of migrating cells, which contribute to drive the organization of the prosencephalon, but also to form a part of the central neuroendocrine compartments. Some cell types are seemingly transient and can play a role in the establishment of the final connections. The understanding of the mechanisms involved in the migration and differentiation of these cell populations can give an insight on the interplay between peripheral structures and central nervous system and on the mechanisms of commitment, phenotype selection and control for neuroendocrine cells able to selectively "colonize" the brain.

Animals↗
PubMed2005

Male-specific cell migration into the developing gonad is a conserved process involving PDGF signalling.

Male-specific migration of cells from the mesonephric kidney into the embryonic gonad is required for testis formation in the mouse. It is unknown, however, whether this process is specific to the mouse embryo or whether it is a fundamental characteristic of testis formation in other vertebrates. The signalling molecule/s underlying the process are also unclear. It has previously been speculated that male-specific cell migration might be limited to mammals. Here, we report that male-specific cell migration is conserved between mammals (mouse) and birds (quail-chicken) and that it involves proper PDGF signalling in both groups. Interspecific co-cultures of embryonic quail mesonephric kidneys together with embryonic chicken gonads showed that quail cells migrated specifically into male chicken gonads at the time of sexual differentiation. The migration process is therefore conserved in birds. Furthermore, this migration involves a conserved signalling pathway/s. When GFP-labelled embryonic mouse mesonephric kidneys were cultured together with embryonic chicken gonads, GFP+ mouse cells migrated specifically into male chicken gonads and not female gonads. The immigrating mouse cells contributed to the interstitial cell population of the developing chicken testis, with most cells expressing the endothelial cell marker, PECAM. The signalling molecule/s released from the embryonic male chicken gonad is therefore recognised by both embryonic quail and mouse mesonephric cells. A candidate signalling molecule mediating the male-specific cell migration is PDGF. We found that PDGF-A and PDGF receptor-alpha are both up-regulated male-specifically in embryonic chicken and mouse gonads. PDGF signalling involves the phosphotidylinositol 3-kinase (PIK3) pathway, an intracellular pathway proposed to be important for mesonephric cell migration in the mammalian gonad. We found that a component of this pathway, PI3KC2alpha, is expressed male-specifically in developing embryonic chicken gonads at the time of sexual differentiation. Treatment of organ cultures with the selective PDGF receptor signalling inhibitor, AG1296 (tyrphostin), blocked or impaired mesonephric cell migration in both the mammalian and avian systems. Taken together, these studies indicate that a key cellular event in gonadal sex differentiation is conserved among higher vertebrates, that it involves PDGF signalling, and that in mammals is an indirect effect of Sry expression.

Animals↗
PubMed2004

Flavonoids promote cell migration in nontumorigenic colon epithelial cells differing in Apc genotype: implications of matrix metalloproteinase activity.

Colonic epithelial cell migration is required for movement up to the apex of the crypt and, hence, normal differentiated cell function. This migratory phenotype is dependent upon wild-type adenomatous polyposis coli (Apc) expression. The purpose of this study is to determine whether specific flavonoids induce cell migration in colon epithelial cells either wild type or heterozygous for Apc genotype. Nontumorigenic murine colon epithelial cell lines with distinct Apc genotypes, young adult mouse colon (YAMC; Apc+/+) cells, and Immortomouse/Min colon epithelial (IMCE; Apc(Min/+)) cells were used to assess the ability of specific flavonoids to induce cell migration relative to migration induced by hepatocyte growth factor (HGF). The citrus flavanones naringenin and hesperetin did not induce cell migration comparable with HGF in either cell type. However, the glycosylated forms of these flavanones, naringin and hesperidin, induced migration differentially in YAMC and IMCE cells. Specifically, naringin and hesperidin induced the greatest migratory response in IMCE cells at 1 microM (P < 0.01) and induced migration greater than untreated control cells (P < 0.05) but equal to HGF-treated cells. In YAMC cells, hesperidin did not induce migration except at the 100-microM concentration. Apigenin induced migration in IMCE cells at 1 (P < 0.05) and 50 microM (P < 0.01) and did not induce migration in the YAMC cells. Catechin induced migration at the highest concentration (300 microM) only in the IMCE cells, whereas epicatechin induced migration at the lowest concentration only (1 microM) in IMCE cells. Overall, the glycosylated citrus flavanones induced the greatest migratory response at the lowest concentration in IMCE cells. Co-treatment of IMCE cells with the global matrix metalloproteinase (MMP) inhibitor Ilomastat in the presence of naringin, hesperidin, or apigenin demonstrated that flavonoid-induced migration was dependent on MMP activity. Induction of the migratory phenotype by flavonoids in these models of preneoplastic epithelial cells suggests a novel mechanism for colon cancer prevention.

Animals↗