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Constitutively migrating malignant rat liver epithelial cells produce a migration-stimulating activity for epithelial cells (eMSA).

Constitutively migrating malignant rat liver epithelial cells obtained by Ha ras transformation exhibit a fibroblastoid phenotype in vitro. The cells deposit the anti-adhesive extracellular matrix (ECM) protein tenascin into their ECM migration tracks. The serum-free medium conditioned by these constitutively migrating cells contains an epithelial migration-stimulating activity (eMSA) that is neither cell-type-, nor species-specific. This eMSA fractionates in the range of 30 to 50 kDa and binds to Mono-Q, Mono-S, and with low affinity to heparin-Sepharose. The conditioned medium also induces the expression of the serine proteinase inhibitor PAI-1. Both migration and expression of PAI-1 are inhibited by cyclic AMP, as previously shown for the migration of the non-transformed liver epithelial cells induced by several growth factors that act through tyrosine kinase receptors. These results suggest that the eMSA might act through signal transduction pathways similar to those of the growth factors previously studied. It is postulated that the eMSA, through both autocrine and paracrine mechanisms, is at least partially responsible for the malignant phenotype of the transformants.

Animals↗

Gated migration: neurons migrate on but not onto substrates containing S-laminin.

Components of the extracellular matrix influence migration of diverse cell types. Some, such as laminin, promote neuronal migration, whereas others are nonpermissive or inhibitory. Here, we demonstrate that a recombinant fragment of s-laminin, a homologue of the laminin B1 chain, is a barrier to neuronal migration. NSC-34 (motoneuron-like) and ciliary ganglion cells were plated on substrates coated with alternating stripes of laminin and a mixture of laminin plus s-laminin. On these patterned substrates, cells seldom crossed from s-laminin-free to s-laminin-containing regions. Mutation of the tripeptide LRE, an adhesive site in s-laminin, abolished s-laminin's ability to block border crossing. However, overall rates of migration were similar on the two substrates. This behavior contrasts with that of previously reported barrier molecules, which decreases rates of cell migration when mixed with permissive substrates. Instead, s-laminin appears to block cell migration through a "gating" mechanism that acts primarily at borders.

Amino Acid Sequence↗

PTSD and depression in refugee children: associations with pre-migration trauma and post-migration stress.

This paper describes the effect of pre-migration and post-migration experiences on the mental health of a sample of 40 refugee children aged 8-16 who lived in London with at least one parent or a refugee relative. Children's post-traumatic stress disorder (PTSD) and depression symptoms were assessed with standardised self-report measures (Impact of Event Scale and Depression Self-Rating Scale for Children, respectively). Information regarding past and present experiences were gathered during an interview with parents. There was a significant correlation between the number of pre-migration traumas experienced by the families and the children's PTSD scores. There was also a significant correlation between the families' number of post-migration stresses and children's depression scores. Higher PTSD scores were significantly associated with the pre-migration experience of violent death of family members and the post-migration experience of an insecure asylum status. Higher depression scores were significantly associated with insecure asylum status and severe financial difficulties. The clinical implications of these findings are discussed.

Adolescent↗

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↗

Protein migration from transplanted nuclei in Amoeba proteus. I. The relation to the cell cycle and RNA migration, as studied by autoradiography.

Autoradiography has been used to examine the migration of proteins from a radioactively labelled amoeba nucleus following transplantation into an unlabelled homophasic amoeba. Nuclei were transferred at three times in the cell cycle coinciding with DNA synthesis (4 h post-division); a peak of RNA synthesis (25 h); and a relative lull in synthetic activity (43 h). Six amino acids were added individually to the culture medium to label the nuclear proteins. Migration of the proteins from the donor nucleus was found to be greatest following the transfer of [3H]aspartic acid-labelled nuclei and least with protein labelled with the basic amino acids. All amino acids exhibited the greatest extent of migration following the 25-h transfers, i.e., coinciding with a peak of RNA synthesis at 26-27.5 h. Actinomycin D (actD) inhibition of RNA synthesis reduced, but did not eliminate the extent of protein migration from the transplanted nucleus, thus indicating the existence of two classes of migratory proteins. Firstly, proteins, associated with RNA transport, which migrated mainly into the host cytoplasm. The second class migrated into the host nucleus from the transplanted nucleus, irrespective of RNa synthesis. The shuttling character of the latter class of proteins is consistent with a role of regulation of nuclear activity.

Amoeba↗

Laminin-5 promotes adhesion and migration of epithelial cells: identification of a migration-related element in the gamma2 chain gene (LAMC2) with activity in transgenic mice.

The effects of laminin-5 and its subunit gamma2 chain on cell adhesion and migration were studied, and a migration-related cis-acting element was identified in the gamma2 chain gene (LAMC2) using promoter-reporter gene constructs in transgenic mice. Intact laminin-5 molecules, but not recombinant gamma2 chain promoted cell adhesion of human keratinocytes and mouse squamous carcinoma cells, indicating that the gamma2 chain does not contain a cellular binding site. However, the gamma2 chain as such is probably involved in the process of cell locomotion, as antibodies against the short arm of the chain inhibited migration of carcinoma cells in an in vitro assay. Further evidence for the involvement of the gamma2 chain in cell migration was obtained by the identification of a cis-acting element in a promoter-lacZ reporter gene construct that was active in migratory epithelial cells of healing wounds in mice made transgenic by microinjection of the construct into fertilized oozytes. The migration active element was located in the sequence between -613 and +55. The same construct, and another one containing 5900 base pairs of the 5' flanking region, yielded very limited expression in cells of normal tissues. The limited expression was, however, only observed in epithelial cells of different tissues, i.e. cell types that normally express laminin-5 in vivo. The results show that the sequence between -613 and +55 contains elements that can drive expression during epithelial cell migration and that also partially confers more general epithelium expression. However, elements outside -5900 and +55 are needed for normal epithelium expression of the LAMC2 gene.

Animals↗

Erythropoietin promotes MCF-7 breast cancer cell migration by an ERK/mitogen-activated protein kinase-dependent pathway and is primarily responsible for the increase in migration observed in hypoxia.

Recent studies indicate that cancer cells express erythropoietin receptor (EpoR). In this study, we have shown that erythropoietin (Epo) activates the mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), and promotes migration in MCF-7 breast cancer cells. Epo-stimulated MCF-7 cell migration was blocked by the MEK inhibitor PD098059 and by dominant negative MEK-1, indicating an essential role for ERK. When MCF-7 cells were exposed to hypoxia (1.0% O(2)) for 3 h, the Epo mRNA level increased 2.4 +/- 0.5-fold, the basal level of ERK activation increased, and cell migration increased 2.0 +/- 0.1-fold. Soluble EpoR and Epo-neutralizing antibody significantly inhibited hypoxia-induced MCF-7 cell migration, suggesting a major role for autocrine EpoR cell signaling. MCF-7 cell migration under hypoxic conditions was also inhibited by PD098059. These experiments identify a novel pathway by which exogenously administered Epo, and Epo that is produced locally by cancer cells under hypoxic conditions, may stimulate cancer cell migration.

Breast Neoplasms↗

Migration from plasticized films into foods. 5. Identification of individual species in a polymeric plasticizer and their migration into foods.

To assess the significance of migration of polymeric plasticizers into foods, chemical characterization and quantification of individual oligomeric species is required. This paper reports the identification of seven individual oligomers isolated from a poly(butylene adipate) plasticizer. Based on mass spectrometry, NMR and chemical degradation, the oligomers were identified as a series of diol-terminated units ranging from a trimer up to an 11-monomer unit, along with a cyclic tetramer, all in the molecular weight range of 300-1100. A study of the migration of polymeric plasticizer from PVC film into olive oil indicated preferential migration of low molecular weight species. These oligomers which comprised 24% of the parent plasticizer contributed more than 90% of the plasticizer migration with the smallest oligomers migrating 90-fold more readily than the bulk of the plasticizer. From a knowledge of total polymeric plasticizer migration from PVC films under actual conditions of food-use, the abundance of individual oligomers in the foods has been estimated.

Adipates↗

PVC cling film in contact with cheese: health aspects related to global migration and specific migration of DEHA.

Following exposure to the food simulant olive oil for 10 days at 5, 20 or 40 degrees C a global migration ranging from 20 to 30 mg/dm2 was detected from a common 'low migration' PVC film plasticized with a mixture of di-(ethylhexyl)adipate (DEHA) and a polymeric plasticizer. In a laboratory experiment samples of cheese of the types most commonly consumed in Denmark were wrapped in this 'low migration' PVC film using a procedure simulating the actual pattern of use in retail shops. After a storage time of 2 h at 5 degrees C the level of DEHA was 45 mg/kg of cheese, which after 10 days increased to 150 mg DEHA per kg of cheese, corresponding to an estimated specific migration of 12 mg DEHA/dm2 of cheese surface. Based on statistics on dietary habits it is concluded that the retail packaging of small portions of cheese even in a 'low migration' PVC cling film may lead to consumer intakes of DEHA close to or above the tolerable daily intake of 0.3 mg/kg body weight as defined by the EEC Scientific Committee for Food. Furthermore, it is stressed that measurements of global migration followed by uncritical use of reduction factors may result in erroneous evaluation of the suitability of DEHA-plasticized cling film for the packaging of fatty foods.

Adipates↗

Japanese migration in contemporary Japan: economic segmentation and interprefectural migration.

This paper examines the economic segmentation model in explaining 1985-86 Japanese interregional migration. The analysis takes advantage of statistical graphic techniques to illustrate the following substantive issues of interregional migration: (1) to examine whether economic segmentation significantly influences Japanese regional migration and (2) to explain socioeconomic characteristics of prefectures for both in- and out-migration. Analytic techniques include a latent structural equation (LISREL) methodology and statistical residual mapping. The residual dispersion patterns, for instance, suggest the extent to which socioeconomic and geopolitical variables explain migration differences by showing unique clusters of unexplained residuals. The analysis further points out that extraneous factors such as high residential land values, significant commuting populations, and regional-specific cultures and traditions need to be incorporated in the economic segmentation model in order to assess the extent of the model's reliability in explaining the pattern of interprefectural migration.

Adolescent↗

Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis.

PURPOSE: The present review aims to emphasize that malignant gliomas are characterized by the diffuse invasion of distant brain tissue by a myriad of single migrating cells that exhibit decreased levels of apoptosis (programmed cell death type I), thus a resistance to cytotoxic insult. METHODS: The present review surveys the molecular mechanisms of migration in malignant gliomas and potential issues arising from treatments, in addition to relationships between glioma cell migration and resistance to apoptosis in terms of the molecular signaling pathways. RESULTS: Clinical and experimental data demonstrate that glioma cell migration is a complex combination of multiple molecular processes, including the alteration of tumor cell adhesion to a modified extracellular matrix, the secretion of proteases by the cells, and modifications to the actin cytoskeleton. Intracellular signaling pathways involved in the acquisition of resistance to apoptosis by migrating glioma cells concern PI3K, Akt, mTOR, NF-kappaB, and autophagy (programmed cell death type II). CONCLUSION: A number of signaling pathways can be constitutively activated in migrating glioma cells, thus rendering these cells resistant to cytotoxic insults. However, these pathways are not all constitutively activated at the same time in any one glioma. Particular inhibitors should therefore only be chosen if the target is present in the tumor tissue, but this is only possible if individual patients are submitted to the molecular profiling of their tumors before undergoing any treatment to combat their migratory glioma cells. Specific antimigratory compounds should be added to conventional radio- and/or chemotherapy.

Apoptosis↗

Interferon-gamma inhibits T84 epithelial cell migration by redirecting transcytosis of beta1 integrin from the migrating leading edge.

Intestinal inflammation is associated with epithelial damage and formation of mucosal wounds. Epithelial cells migration is required for wound closure. In inflammatory status, migrating epithelial cells are exposed to proinflammatory cytokines such as IFN-gamma. However, influence of such cytokines on intestinal epithelial wound closure remains unknown. The present study was designed to investigate the effect of IFN-gamma on migration of model T84 intestinal epithelial cells and recovery of epithelial wounds. IFN-gamma significantly inhibited rate of T84 cell migration and closure of epithelial wounds. This effect was accompanied by the formation of large aberrant lamellipodia at the leading edge as well as significant decrease in the number of beta(1) integrin containing focal adhesions. IFN-gamma exposure increased endocytosis of beta(1) integrin and shifted its accumulation from early/recycling endosomes at the leading edge to a yet unidentified compartment at the cell base. This redirection in beta(1) integrin transcytosis was inhibited by depolymerization of microtubules with nocodazole and was unaffected by stabilization of microtubules with docetaxel. These results suggest that IFN-gamma attenuates epithelial wound closure by microtubule-dependent redirection of beta(1) integrin transcytosis from the leading edge of migrating cells thereby inhibiting adequate turnover of focal adhesion complexes and cell migration.

Cell Line↗

Eosinophil transendothelial migration induced by cytokines. I. Role of endothelial and eosinophil adhesion molecules in IL-1 beta-induced transendothelial migration.

IL-1 beta promotes adhesiveness in human umbilical vein endothelial cells (HuVEC) for eosinophils through expression of adhesion molecules including intercellular adhesion molecules-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). Using an in vitro endothelial monolayer system, we examined whether IL-1 beta or TNF-alpha can promote eosinophil transendothelial migration. We also evaluated the contributions of ICAM-1, E-selectin, VCAM-1, leukocyte adhesion complex (CD11/18), and very late Ag-4 (CD11b/18) (VLA-4) in this process using blocking mAb, and determined the changes in expression of CD11b and L-selectin on eosinophils that had undergone transmigration. IL-1 beta and TNF-alpha treatment of HuVEC (4 h, 5 ng/ml) induced significant transendothelial migration of eosinophils (a 4.1 +/- 0.4-fold (IL-1 beta) and 2.0 +/- 0.9-fold (TNF-alpha) increase from the spontaneous value of 3.2 +/- 0.3%). Increased CD11b expression and shedding of L-selectin were observed on eosinophils following IL-1 beta-induced eosinophil transendothelial migration. Studies with mAb revealed that blockade of either ICAM-1 or CD11/18 inhibited transmigration, while antibodies against VCAM-1 and VLA-4 had no inhibitory effect. Among antibodies which block beta 2 integrins, anti-CD18 mAb had the best inhibitory effect (88% inhibition). The combined inhibitory effect of anti-CD11a mAb and anti-CD11b mAb was roughly equal to that of anti-CD18, although anti-CD11a (31% inhibition) and anti-CD11b (52% inhibition) were less effective individually. Anti-ICAM-1 by itself inhibited IL-1 beta-induced eosinophil transendothelial migration (24% inhibition) whereas neither anti-E-selectin nor anti-VCAM-1 were effective inhibitors. Interestingly, the combination of anti-E-selectin and anti-VCAM-1 with anti-ICAM-1 inhibited IL-1 beta-induced eosinophil transendothelial migration significantly better (53% inhibition) than anti-ICAM-1 alone. These results suggest that although the initial attachment of eosinophils to IL-1 beta-activated endothelial cells involves VCAM-1, E-selectin, and ICAM-1, the subsequent transendothelial migration process relies heavily on ICAM-1 and CD11/18. Finally, the changes that eosinophils have been observed to undergo during infiltration in vivo, namely increased expression of CD11/18 and shedding of L-selectin, appear to take place as a direct result of the interaction between eosinophils and endothelial cells.

Antibodies, Monoclonal↗

In vitro modulation of human leucocyte migration and migration inhibitory factor (LIF) activity by cyclic 3',5'-AMP and cyclic 3',5'-GMP.

The effects of cyclic 3', 5'-AMP (cAMP) and cyclic 3', 5'-GMP (cGMP) on the in vitro migration of human peripheral blood leucocytes under agarose and on the activity of leucocyte migration inhibitory factor (LIF) was studied. Leucocyte migration was not influenced by dibutyryl cAMP, while the dibutyryl derivative of cGMP significantly stimulated cell migration (1 x 10(-5)M). LIF-treated leucocytes partially escaped migration inhibition in the presence of dibutyryl cAMP (greater than or equal to 1 x 10(-6)M), while dibutyryl cGMP was inefficient. If the parent compounds cAMP and cGMP were tested, almost similar results would be obtained, although at higher concentrations of the drugs. These results represent initial experiments with a view to investigating the possible role of cyclic nucleotides in the expression of LIF activity.

Bucladesine↗

Estimation of place-to-place migration flows from net migration totals: a minimum information approach.

"A truism in demography has been that net migration may be derived from information on gross place-to-place flows, but that gross place-to-place flows cannot be inferred back from information on the net population movements in a system. Some recent work on maximum entropy and minimum information models, however, suggests a possible means for estimating just such as set of place-to-place flows. The net migration constrained model presented here could prove particularly useful for updating detailed migration matrices on the basis of current net migration estimates, and could even provide some clues as to the nature of the still poorly understood relationship between gross and net migration. Performance of the model is demonstrated using flow matrices from the 1960 and 1970 U.S. Censuses.

Americas↗

Migrating to learn and learning to migrate: a study of the experiences and intentions of international student migrants.

"The research reported here evaluates whether students come to the UK mainly for educational reasons, and therefore perceive their stay as temporary, or whether emigration for study is being used as part of a conscious strategy by people intending to become future labour migrants.... The simplest interpretation of the results appears to be that migration, experienced as a result of international moves for study purposes, does not influence planning of further migration moves. But the research also indicates that migration for education is closely tied to other types of population redistribution and should be treated by population geographers as an integral part of international migration systems." Data were collected by questionnaire survey from 349 engineering students at Hong Kong universities and 82 Hong Kong students studying engineering in the UK.

Asia↗

Macrophage migration inhibitory factor: roles in regulating tumor cell migration and expression of angiogenic factors in hepatocellular carcinoma.

Macrophage migration inhibitory factor (MIF) may contribute to multiple aspects of tumor progression, including control of cell proliferation, differentiation, cell survival and angiogenesis. However, the potential roles of MIF in regulating hepatocellular carcinoma (HCC) tumor cell migration and the expression of angiogenic factors by HCC tumor cells have not been studied yet. In our study, we reported that intracellular MIF mRNA and protein were overexpressed in HCC tissues compared to nontumor tissues by using in situ hybridization and immunohistochemic staining. HCC tumor cell lines also secreted large amounts of MIF into the supernatants of tumor cell culture. To assess the role of MIF in HCC, we employed the transwell invasion chamber to study the effect of MIF on tumor cell migration. Our results showed that recombinant MIF and the supernatants of tumor cell line culture could enhance the invasion and migration of HCC cells. This effect can be inhibited by the addition of a neutralizing anti-MIF antibody. We observed that increased MIF serum levels correlated with higher levels of interleukin-8 (IL-8) in the sera of patients with HCC than in normal volunteers. We therefore hypothesized that MIF may regulate the production of angiogenic factors by HCC cells. To test this hypothesis, we examined the effect of MIF treatment on vascular endothelial growth factor (VEGF) and IL-8 expression by HCC cell lines. MIF induced a significant dose-dependent increase in IL-8 and VEGF production. Taken together, our results indicated that MIF may act as an autocrine-acting factor that stimulates angiogenesis and metastasis in HCC by promoting expression of angiogenic factors and migration of tumor cells. A more detailed understanding of the MIF regulatory mechanisms involved may provide insight into new direction in the treatment of HCC.

Adult↗

Modulation of lymphocyte migration by human lymphokines. III. Characterization of a lymphocyte migration inhibitory factor (LyMIF35K).

The lymphokine that augments the migration of nonsensitized T lymphocytes (LCF) has been observed to be predominantly a chemokinetic factor, suggesting that separate lymphocyte migration inhibitory lymphokine(s) might exist. Utilizing a modified Boyden chamber assay, lymphocyte migration inhibitory activity was identified in the culture supernatants of human nylon wool-nonadherent blood mononuclear cells stimulated with concanavalin A in vitro for 48 hr. Sephadex G-100 gel filtration chromatography of these culture supernatants was shown to contain two regions of noncytotoxic migration inhibitory activity for nonsensitized human blood lymphocytes and rat splenic lymphocytes. The 30-40,000 dalton inhibitory activity was further characterized and noted to be cationic by ion-exchange chromatography and isoelectric focusing (pI = 8.6). Its biologic activity was sensitive to neuraminidase and to heat treatment but not to trypsin. The migration inhibitory activity of this factor (LyMIF35K) was directly proportional to its ability to increase lymphocyte adherence.

Animals↗