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PubMed1992

Dermal tumour necrosis factor-alpha induces dendritic cell migration to draining lymph nodes, and possibly provides one stimulus for Langerhans' cell migration.

Previous studies have shown that following skin sensitization there is an accumulation of dendritic cells (DC) in lymph nodes draining the site of exposure. A significant number of the DC which arrive in the lymph nodes bear high levels of antigen, and the available evidence indicates that they are derived from epidermal Langerhans' cells (LC). Although freshly isolated LC are relatively inefficient antigen-presenting cells, the antigen-bearing DC which are found within draining nodes following skin sensitization are highly immunostimulatory. Recent investigations indicate that the functional maturation of LC as they migrate from the skin is reflected by an enhanced capacity to form stable clusters with lymphocytes, and is associated with an increased expression of membrane major histocompatibility complex (MHC) class II (Ia) antigen. By analogy with in vitro studies of LC maturation, it is possible that such changes are effected by granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-1 (IL-1), both of which are products of epidermal cells. The question remains as to the nature of the stimulus that initiates LC migration. In the present study we have examined in mice the effects of intradermal injection of tumour necrosis factor-alpha (TNF-alpha), another epidermal cytokine, on the accumulation of DC in lymph nodes. Murine recombinant TNF-alpha was found to cause a concentration- and time-dependent increase in the number of DC within draining nodes. Under the same conditions of exposure murine recombinant GM-CSF was without effect. Heat treatment of mouse TNF-alpha resulted in an equivalent inhibition of both DC accumulation and cytotoxic activity measured by in vitro bioassay. An interesting observation was that equal concentrations of human TNF-alpha, of equivalent specific activity, failed to influence the frequency of lymph node DC. These data demonstrate that TNF-alpha induces DC accumulation in draining lymph nodes, and we propose that this cytokine may provide one stimulus for LC migration during cutaneous immune responses.

Animals↗
PubMed2005

Ca2+ influx through L-type Ca2+ channels controls the trailing tail contraction in growth factor-induced fibroblast cell migration.

Growth factor-induced cell migration underlies various physiological and pathological processes. The mechanisms by which growth factors regulate cell migration are not completely understood. Although intracellular elevation of Ca2+ is known to be critical in cell migration, the source of this Ca2+ elevation and the mechanism by which Ca2+ modulates this process in fibroblast cells are not well defined. Here we show that increase of cellular Ca2+ through Ca2+ influx, rather than Ca2+ release from intracellular stores, is essential for growth factor-induced fibroblast cell migration. Voltage-gated L-type Ca2+ channels, previously known to exist in excitable cells such as neurons and muscle cells, are shown here to be present in fibroblasts as well. Furthermore, these channels are responsible for the Ca2+ influx. L-type Ca2+ channel inhibitors block growth factor-induced Ca2+ influx and fibroblast cell migration. One mechanism by which Ca2+ signals control cell migration is to regulate the contraction of the trailing edge of migrating fibroblasts; this process is controlled by the small GTPase Rho in fast migrating cells such as leukocytes. Downstream of Ca2+, both calmodulin and myosin light chain kinase, but not calcineurin, are involved leading to phosphorylation of the myosin light chain at the trailing end. Thus, trailing edge contraction is critically regulated by Ca2+ influx through L-type Ca2+ channels in growth factor-induced fibroblast cell migration.

Animals↗
PubMed2004

Tissue inhibitor of metalloproteinases-4 suppresses vascular smooth muscle cell migration and induces cell apoptosis.

In a previous study, we have demonstrated that overexpression of the tissue inhibitors of metalloproteinases-4 (TIMP-4) can inhibit the neointima formation in the rat carotid model. To define the functions of tissue inhibitor of metalloproteinases-4 (TIMP-4) in SMCs, we transduced human TIMP-4 cDNA into rat aortic SMCs by using adenoviral vector. Overexpression of TIMP-4 blocked the conversion of pro-MMP-2 to the active form and inhibited basic fibroblast growth factor-induced migration by 56.7% (p < 0.01). Overexpression of TIMP-4 markedly increased apoptotic cell death without changing their proliferation. Importantly, overexpression of human TIMP-4 in the wall of balloon-injured rat carotid artery also increased SMC apoptosis. The percentages of TUNEL-positive cells of total cells increased significantly in AdTIMP-4 infected group compared with AdGFP infected group. These findings demonstrate that TIMP-4 can inhibit SMCs migration and induce apoptosis in vitro and in vivo, which may generate new targets for prevention and treatment of vascular diseases.

Angioplasty, Balloon↗
PubMed1999

A critical role for a peritumoral stromal reaction in the induction of T-cell migration responsible for interleukin-12-induced tumor regression.

Interleukin (IL) 12 has been shown to elicit tumor regression when this cytokine induces the migration of T cells to tumor sites. The present study investigates the role of a peritumoral stromal reaction in IL-12-induced T-cell migration. In the CSA1M and OV-HM tumor models, IL-12 treatment induced tumor regression that is associated with T-cell migration. Neither T-cell migration nor tumor regression was observed in the Meth A and MCH-1-A1 models. Stromal tissue containing neovascular blood vessels developed at the peritumoral area of the former two IL-12-responsive tumors but not at the peritumoral area of the latter two IL-12-unresponsive tumors. The significance of stroma development was investigated using a pair of tumor models (CSA1M and a subline derived from CSA1M designated the CSA1M variant), both of which exhibit the same tumor immunogenicity. In contrast to the parental CSA1M cell line, the variant cell line was not responsive to IL-12, and neither stroma development nor T-cell migration was observed, even after IL-12 treatment. Histological analyses revealed that the parental cell line had peritumoral stroma with intrastromal vessels but only a few vessels in tumor parenchyma, whereas the variant cell line showed no stroma but had abundant vasculature in the tumor parenchyma. Most importantly, only stromal vessels in the parental tumors expressed detectable and enhanced levels of vascular cell adhesion molecule 1 (VCAM-1)/ intercellular adhesion molecule 1 (ICAM-1) before and after IL-12 treatment, respectively. In contrast, parenchymal vasculature in the variant cell line failed to express VCAM-1/ICAM-1 even after IL-12 treatment. When transferred into recipient tumor-bearing mice, IL-12-stimulated T cells from the parental CSA1M-bearing or the variant CSA1M-bearing mice migrated into the parental but not into the variant tumor mass. Together with our previous finding that T-cell migration depends on the VCAM-1/ICAM-1 adhesive interactions, the present results indicate a critical role for peritumoral stroma/stromal vasculature in the acceptance of tumor-infiltrating T cells that is a prerequisite for IL-12-induced tumor regression.

Animals↗
PubMed2005

Novel role for PDEF in epithelial cell migration and invasion.

Cell migration and invasion are two critical cellular processes that are often deregulated during tumorigenesis. To identify factors that contribute to oncogenic progression by stimulating cell migration, we conducted a powerful retroviral based migration screen using an MCF7 cDNA library and the immortalized human breast epithelial cell line MCF-10A. We identified prostate derived Ets factor (PDEF), an Ets transcription factor that is overexpressed in both prostate and breast carcinoma, as a candidate promigratory gene from this screen. Whereas PDEF induced limited motility of MCF-10A cells, coexpression of PDEF with the receptor tyrosine kinases (RTK) ErbB2 and colony-stimulating factor receptor (CSF-1R)/CSF-1 significantly enhanced MCF-10A motility. Furthermore, cells coexpressing PDEF with either ErbB2 or CSF-1R/CSF-1 induced a dramatic invasive phenotype in three-dimensional cultures. Constitutive activation of the extracellular signal-regulated kinase (ERK) pathway also enhanced PDEF-induced motility and invasion, suggesting that activation of the ERK/mitogen-activated protein kinase by ErbB2 and CSF-1R/CSF-1 can cooperate with PDEF to promote motility and invasion. Furthermore, PDEF promoted anchorage-independent growth of ErbB2 and CSF-1R/CSF-1-expressing cells. Using laser capture microdissection, we also found that PDEF mRNA is overexpressed in breast tumor epithelia throughout tumor progression. Taken together, these findings suggest that the transcription factor PDEF may play an important role in breast tumorigenesis and that PDEF overexpression may be particularly significant in tumors that exhibit activation of oncogenic RTKs such as ErbB2 and CSF-1R.

Breast Neoplasms↗
PubMed2002

CD44v10 interaction with Rho-kinase (ROK) activates inositol 1,4,5-triphosphate (IP3) receptor-mediated Ca2+ signaling during hyaluronan (HA)-induced endothelial cell migration.

Aortic endothelial cells (GM7372A) express a major cell adhesion molecule, CD44v10, which binds the extracellular matrix component, hyaluronan (HA), at its external domain and interacts with various signaling molecules at its cytoplasmic domain. In this study, we have determined that CD44v10 and Rho-Kinase (ROK) are physically associated as a complex in vivo. Using a recombinant fragment of ROK (in particular, the pleckstrin homology [PH] domain) and in vitro binding assays, we have detected a specific binding interaction between the PH domain of ROK and the cytoplasmic domain of CD44. Scatchard plot analysis indicates that there is a single high-affinity CD44 binding site in the PH domain of ROK with an apparent dissociation constant (Kd) of 1.76 nM, which is comparable to CD44 binding (Kd approximately 1.56 nM) to intact ROK. These findings suggest that the PH domain is the primary ROK binding region for CD44. Furthermore, HA binding to GM7372A cells promotes RhoA-mediated ROK activity, which, in turn, increases phosphorylation of three different inositol 1, 4, 5-trisphosphate receptors (IP(3)Rs) [in particular, subtype 1 (IP(3)R1), and to a lesser extent subtype 2 (IP(3)R2) and subtype 3 (IP(3)R3)] all known as IP(3)-gated Ca(2+) channels. The phosphorylated IP(3)R1 (but not IP(3)R2 or IP(3)R3) is enhanced in its binding to IP(3) which subsequently stimulates IP(3)-mediated Ca(2+) flux. Transfection of the endothelial cells with ROK's PH cDNA significantly reduces ROK association with CD44v10, and effectively inhibits ROK-mediated phosphorylation of IP(3)Rs and IP(3)R-mediated Ca(2+) flux in vitro. The PH domain of ROK also functions as a dominant-negative mutant in vivo to block HA-dependent, CD44v10-specific intracellular Ca(2+) mobilization and endothelial cell migration. Taken together, we believe that CD44v10 interaction with ROK plays a pivotal role in IP(3)R-mediated Ca(2+) signaling during HA-mediated endothelial cell migration.

Animals↗
PubMed2002

Differential regulation of cell migration, actin stress fiber organization, and cell transformation by functional domains of Crk-associated substrate.

The Crk-associated substrate (Cas) is a unique docking protein that possesses a repetitive stretch of tyrosine-containing motifs and an Src homology 3 (SH3) domain. Embryonic fibroblasts lacking Cas demonstrated resistance to Src-induced transformation along with impaired actin bundling and cell motility, indicating critical roles of Cas in actin cytoskeleton organization, cell migration, and oncogenesis. To gain further insight into roles of each domain of Cas in these processes, a compensation assay was performed by expressing a series of Cas mutants in Cas-deficient fibroblasts. The results showed that motifs containing YDxP were indispensable for actin cytoskeleton organization and cell migration, suggesting that CrkII-mediated signaling regulates these biological processes. The C-terminal Src-binding domain played essential roles in cell migration and membrane localization of Cas, although it was dispensable in the organization of actin stress fibers. Furthermore, the Src-binding domain was also a prerequisite for Src transformation possibly, because of its crucial role in the phosphorylation of Cas during transformation. Overall, differential uses of the Cas domains in individual biological processes were demonstrated.

Actins↗
PubMed1993

Microinjection of antifibronectin antibodies in the chicken blastoderm: inhibition of mesoblast cell migration but not of cell ingression at the primitive streak.

The involvement of fibronectin in adhesion and migration of individual mesoblast cells during chicken gastrulation was examined after microinjection of functional and nonfunctional antifibronectin antibodies in the blastoderm during the period of rapid migration of mesoblast cells. The injection of affinity-purified polyclonal antihuman fibronectin antibody (total IgG or Fab fragment) or of monoclonal antichicken cellular fibronectin caused a thickening of the primitive streak, which was composed of loosely connected cells. This effect was most evident at the level of Hensen's node, and very few mesoblast cells were observed migrating in the space between upper layer and deep layer. The obvious explanation of this effect was that the de-epithelialization of upper layer cells persisted in the presence of antibodies, but ingressed cells failed to emigrate from the primitive streak. Immunostaining of microinjected antibodies showed binding to the basement membrane, to the cell surface of mesoblast cells that had migrated before microinjection occurred, and to the cell surface of deep layer cells. Cells that ingressed and detached in the course of reincubation of the embryo possessed little immunolabelling along their cell surface. The results suggest that the failure of ingressed cells to emigrate from the primitive streak and to form mesoblast was due (1) to alterations in adhesion between newly ingressed primitive streak cells, which had the ability to detach but possessed relatively little fibronectin along their cell surfaces and a small number of cell protrusions, and (2) probably to a lack of adhesion of detached cells to the basement membrane, which was blocked by the presence of antifibronectin antibodies. We conclude that the presence of fibronectin in the basement membrane is required for emigration of ingressed cells and migration of mesoblast cells to occur. Once migration has commenced, fibronectin is also deposited along the cell surface of migrating cells, a factor that may increase their mutual adhesion.

Animals↗
PubMed2004

p38 Mitogen-activated protein kinase regulation of endothelial cell migration depends on urokinase plasminogen activator expression.

The migration of endothelial cells in response to various stimulating factors plays an essential role in angiogenesis. The p38 MAPK pathway has been implicated to play an important role in endothelial cell migration because inhibiting p38 MAPK activity down-regulates vascular endothelial growth factor (VEGF)-stimulated migration. Currently, the signaling components in the p38 MAPK activation pathway and especially the mechanisms responsible for p38 MAPK-regulated endothelial cell migration are not well understood. In the present study, we found that p38 MAPK activity is required for endothelial cell migration stimulated by both VEGF and nongrowth factor stimulants, sphingosine 1-phosphate and soluble vascular cell adhesion molecule. By using dominant negative forms of signaling components in the p38 MAPK pathway, we identified that a regulatory pathway consisting of MKK3-p38alpha/gamma-MAPK-activated protein kinase 2 participated in VEGF-stimulated migration. In further studies, we showed that a minimum of a 10-h treatment with SB203580 (specific p38 MAPK inhibitor) was needed to block VEGF-stimulated migration, suggesting an indirect role of p38 MAPK in this cellular event. Most interestingly, the occurrence of SB203580-induced migratory inhibition coincided with a reduction of urokinase plasminogen activator (uPA) expression. Furthermore, agents disrupting uPA and uPA receptor interaction abrogated VEGF-stimulated cell migration. These results suggest a possible association between cell migration and uPA expression. Indeed, VEGF-stimulated migration was not compromised by SB203580 in endothelial cells expressing the uPA transgene; however, VEGF-stimulated migration was inhibited by agents disrupting uPA-uPA receptor interaction. These results thus suggest that the p38 MAPK pathway participates in endothelial cell migration by regulating uPA expression.

Actins↗
PubMed1995

Inhibition by cardiac natriuretic peptides of rat vascular endothelial cell migration.

Vascular endothelial cell migration is proposed to be an important process in the initiation and progression of atherosclerosis. We designed the present study to examine the effects of atrial and brain natriuretic peptides on fetal calf serum-stimulated migration of cultured rat aortic endothelial cells using Boyden's chamber method. Fetal calf serum clearly stimulated migration in a concentration- and time-dependent manner. Rat atrial natriuretic peptide-(1-28) and rat brain natriuretic peptide-45, which are the major circulating forms of atrial and brain natriuretic peptides in rats, inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-10) and 10(-6) mol/L. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cGMP. The addition of a cGMP analogue 8-bromo-cGMP, significantly inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-7) and 10(-3) mol/L. Rat atrial natriuretic peptide-(5-25) was much less effective than atrial natriuretic peptide-(1-28) or rat brain natriuretic peptide-45 with respect to inhibiting migration and increasing cGMP levels. These results indicate that atrial and brain natriuretic peptides inhibit fetal calf serum-stimulated vascular endothelial cell migration, probably through a cGMP-dependent process.

Animals↗
PubMed2006

Novel function of IFN-gamma: negative regulation of dendritic cell migration and T cell priming.

IFN-gamma is considered to be a Th1 cytokine with immunomodulatory effects on a variety of immune cells. In this study, we determined whether dendritic cell (DC) function was aberrant in IFN-gamma knockout (GKO) mice. The results demonstrated that IFN-gamma deficiency did not interfere with bone marrow-derived DC development and maturation in vitro. However, functional analysis showed that bone marrow-derived DC from GKO mice had altered cytokine secretion, allostimulatory and Ag presentation capacity, chemokine receptor expression, and in vitro chemotaxis. LPS induced the recruitment of DC from different organs into the spleen; epicutaneously sensitized DC with hapten (FITC) accumulated in the draining lymph nodes and CD11c(+) DC levels in the draining lymph nodes from autoantigen (interphotoreceptor retinoid-binding protein) immunized mice were enhanced in GKO mice as compared with wild-type mice. After treatment of GKO mice with i.p. IFN-gamma injection restored IFN-gamma levels in vivo, DC migration decreased in response to LPS or FITC. IFN-gamma altered the adaptive immune responses in vivo, since T cell priming and IL-2 production were increased in interphotoreceptor retinoid-binding protein-immunized GKO mice. Furthermore, in IFN-gamma-treated GKO mice, experimental autoimmune uveitis score enhancement and T cell activation were eliminated. Taken together, IFN-gamma appears to play a negative regulatory role on in vivo DC function, resulting in suppression of Ag-specific T cell priming.

Animals↗
PubMed2004

[Increased cell migration of nasopharyngeal carcinoma cell lines in vitro by macrophage migration inhibitory factor].

OBJECTIVE: To study whether macrophage migration inhibitory factor (MIF) can increase the ability of invasion of nasopharyngeal carcinoma cell lines in vitro, and to investigate the mechanism of invasion and metastasis of tumor cells during the early stage of nasopharyngeal carcinoma (NPC). METHODS: The invasion and migration of NPC cell lines, CNE-1 and CNE-2, were evaluated by micron-migration assay in a chamber with 8- micro m porosity polycarbonate filter membrane. Flow cytometry and western blotting were adopted respectively to evaluate the protein expression level of matrix metalloproteinase 2 and 9 (MMP2, MMP9) in MIF treated or non-treated tumor cell lines. The concentrations of interleukin 8 (IL-8) secreted into the culture supernatant by the cells were measured by using Enzyme-linked immunoabsorbent assay (ELISA). RESULTS: (1) After treatment with MIF for 24 hours, the number of cells passing through the 8- micro m filter membrane were increased in CNE-1 (113.7 +/- 20.9) and CNE-2 (311.3 +/- 48.9), as compared with that of non-MIF treated NPC cells. A significant statistic difference (P = 0.005, P = 0.001) was obtained in both CNE-1 and CNE-2 cells. (2) After treatment with MIF, the number of MMP9-positive cells increased in both CNE-1 (from 28.5% +/- 2.45% to 82.4% +/- 3.49%, P = 0.001) and CNE-2 (from 32.8% +/- 3.48% to 86.1% +/- 1.62%, P = 0.002) cell lines. In addition, an enhanced MMP9 protein expression up to 3-fold was observed in both cell lines. However, the expression level of MMP2 did not changed significantly between treated and non-treated cell lines (P > 0.05). (3) The concentration of IL-8 in the culture supernatant of CNE-2 was 1201.8 +/- 593.3 pg/ml after treatment with MIF for 24 h, remarkably higher than that without MIF treatment (32.7 +/- 20.1 pg/ml, P = 0.026). A similar change was not detected in CNE-1 (P = 0.581) cells. CONCLUSIONS: (1) MIF can increase cell migration of CNE-1 and CNE-2 NPC cell lines in vitro. (2) A higher expression level of MMP9 and an up-regulated IL-8 by MIF may play a very important role in the progress of NPC, such as invasion and metastasis.

Cell Line, Tumor↗
PubMed2006

mig-5/Dsh controls cell fate determination and cell migration in C. elegans.

Cell fate determination and cell migration are two essential events in the development of an organism. We identify mig-5, a Dishevelled family member, as a gene that regulates several cell fate decisions and cell migrations that are important during C. elegans embryonic and larval development. In offspring from mig-5 mutants, cell migrations are defective during hypodermal morphogenesis, QL neuroblast migration, and the gonad arm migration led by the distal tip cells (DTCs). In addition to abnormal migration, DTC fate is affected, resulting in either an absent or an extra DTC. The cell fates of the anchor cell in hermaphrodites and the linker cells in the male gonad are also defective, often resulting in the cells adopting the fates of their sister lineage. Moreover, 2 degrees vulval precursor cells occasionally adopt the 3 degrees vulval cell fate, resulting in a deformed vulva, and the P12 hypodermal precursor often differentiates into a second P11 cell. These defects demonstrate that MIG-5 is essential in determining proper cell fate and cell migration throughout C. elegans development.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Decorin inhibits cell migration through a process requiring its glycosaminoglycan side chain.

Several studies overwhelmingly support the notion that decorin (DCN) is involved in matrix assembly, and in the control of cell adhesion and proliferation. However, nothing is known about the role of DCN during cell migration. Cell migration is a tightly regulated process which requires both adhesion (at the leading edge of the cell) and de-adhesion (at the trailing edge of the cell) from the substratum. We have determined in this study the effect of DCN on MG-63 osteosarcoma cell migration and have analyzed whether its effect is mediated by the protein core and/or the glycosaminoglycan side chain. DCN impeded the migration-promoting effect of matrix molecules (fibronectin, collagen type I) known to interact with the proteoglycan. Conversely, DCN did not counteract the migration-promoting effect of fibrinogen lacking proteoglycan affinity. DCN bearing dermatan-sulfate chains (i.e., skin and cartilage DCN) was about 20-fold more effective in inhibiting cell migration than DCN bearing chondroitin-sulfate chains (i.e., bone DCN). In addition, chondroitinase AC-treatment of cartilage DCN (which specifically removes chondroitin-sulfate chains) did not attenuate the inhibitory effect of this proteoglycan, while cartilage DCN deprived of both chondroitin- and dermatan-sulfate chains failed to alter cell migration promoted by either fibronectin or its heparin- and cell-binding domains. These data assert that the dermatan-sulfate chains of DCN are responsible for a negative influence on cell migration. However, isolated glycosaminoglycans failed to alter cell migration promoted by fibronectin, indicating that strongly negatively charged glycosaminoglycans alone cannot account for the impaired cell motility seen with DCN. Overall, these results show that the inhibitory action of DCN is dependent of substratum binding, is differentially mediated by its glycosaminoglycan side chains (chondroitin-sulfate vs. dermatan-sulfate chains), and is independent of a steric hindrance effect exerted by its glycosaminoglycan side chains.

Animals↗
PubMedDate not supplied

Digital holographic microscopy for the three-dimensional dynamic analysis of in vitro cancer cell migration.

Cancer cell motility and invasion are critical targets for anticancer therapeutics. Whereas in vitro models could be designed for rapid screening with a view to investigate these targets, careful consideration must be given to the construction of appropriate model systems. Most investigations focus on two-dimensional (2-D) assays despite the fact that increasing evidence suggests that migration across rigid and planar substrates fails to recapitulate in vivo behavior. In contrast, few systems enable three-dimensional (3-D) cell migration to be quantitatively analyzed. We previously developed a digital holographic microscope (DHM) working in transmission with a partially spatial coherence source. This configuration avoids the noise artifacts of laser illumination and makes possible the direct recording of information on the 3-D structure of samples consisting of multiple objects embedded in scattering media, such as cell cultures in matrix gels. The software driving our DHM system is equipped with a time-lapse ability that enables the 3-D trajectories of living cells to be reconstituted and quantitatively analyzed.

Cell Count↗
PubMed1978

On the development of the cerebellum of the trout, Salmo gairdneri. I. Patterns of cell migration.

Patterns of cell migration in the cerebellum of Salmo gairneri RICHARDSON, 1836 were studied in fish ranging in length from 4.5 to 230 mm. Sagittal and transverse series were stained with haematoxylin-eosin or according to Nissl or Golgi. The cerebellum of the trout comprises three main parts, i.e. the massive corpus cerebelli, the folded valvula cerebelli and the transversely oriented lobus vestibulolateralis. The early cerebellar anlage is a simple plate, which is delimited from the tectum mesencephali by the fissura rhombo-mesencephalica. The histogenesis may be divided into three phases. During the first phase the matrix layer produces the mantle layer. During the second phase the three typical cerebellar layers are formed. The third phase is characterized by growth. As regards the first phase, the mantle layer develops throughout almost the entire extent of the cerebellar anlage. Only in a narrow paramedian strip (matrix zone M) this layer does fail to appear. In regions where the mantle layer is formed, the matrix no longer occupies the whole width of the wall and is termed the ventricular matrix. The largest part of the ventricular matrix is gradually exhausted. However, in some places this matrix persists as a layer of proliferating cells. This holds for the matrices of the caudal border of the cerebellum; matrix zone L, surrounding the lateral recesses of the fourth ventricle, and matrix zone P, connecting the matrix zones L. The mantle layer produced in the first phase of histogensis mainly develops into the ganglionic layer. The second phase of histogenesis is characterized by the formation of a secondary matrix. Newly produced cells of the matrix zones M, L and P migrate away from their sites of origin towards the regions where a mantle layer prevsiously has been formed. The majority of these cells develops into granule cells. Migration of the cells produced in the first phase of histogenesis occurs in the radial direction. Because of the curvature of the cerebellum this direction changes with respect to the main longitudinal axis of the brain from region to region. The migration paths of granule cells show variable directions, namely (a) tangential followed by radial, for granule cells in the corpus cerebelli and in the medial parts of the valvula cerebelli and the lobus vestibulolaterialis, (b) tangential, for granule cells in the lateral parts of the valvula and (c) radial, for granule cells in the lateral parts of the lobus vestibulolateralis. The analysis of these migration patterns elucidates both the histogenesis and the morphogenesis of the cerebellum of the trout.

Animals↗
PubMed2007

Enhancement of cell migration by corticotropin-releasing hormone through ERK1/2 pathway in murine melanoma cell line, B16F10.

Melanoma is a malignant skin cancer that displays a high rate of tumor cell migration and metastasis. This study examined how corticotropin-releasing hormone (CRH) affects the migration of melanoma cells in order to further understand the relationship between stress and tumor cell migration. The migration assay data showed that CRH treatment increased the level of B16F10 cell migration in a dose- and time-dependent manner. To determine whether the extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling pathway is involved in the upregulation of melanoma migration, cells were pretreated with an inhibitor of ERK1/2 (PD098059). The pretreatment of PD098059 blocked the increase in cell migration. Furthermore, CRH induced the phosphorylation of ERK1/2. The maximum activation of ERK1/2 by CRH was observed at 15 min. Taken together, these results suggest that CRH is an important mediator that regulates the migration of melanoma cells in the skin during stress through the ERK1/2 signaling pathway.

Animals↗
PubMed2003

Matrix metalloproteinase-2 and -9 differentially regulate smooth muscle cell migration and cell-mediated collagen organization.

OBJECTIVE: Smooth muscle cells (SMCs) produce both matrix metalloproteinase (MMP)-2 and MMP-9, enzymes with similar in vitro matrix degrading abilities. We compared the specific contributions of these enzymes to SMC-matrix interactions in vitro and in vivo. METHODS AND RESULTS: Using genetic models of deficiency, we investigated MMP-2 and MMP-9 roles in SMC migration in vivo in the formation of intimal hyperplasia and in vitro. In addition, we investigated potential effects of MMP-2 and MMP-9 genetic deficiency on compaction and assembly of collagen by SMCs. CONCLUSIONS: MMP-2 and MMP-9 genetic deficiency decreased by 81% and 65%, respectively (P<0.01), SMC invasion in vitro and decreased formation of intimal hyperplasia in vivo (P<0.01). However, we found that MMP-9, but not MMP-2, was necessary for organization of collagen by SMCs. Likewise, we found that MMP-9 deficiency resulted in a 50% reduction of SMC attachment to gelatin (P<0.01), indicating that SMCs may use MMP-9 as a bridge between the cell surface and matrix. Furthermore, we found that the hyaluronan receptor, CD44, assists in attachment and utilization of MMP-9 by SMCs. Understanding the specific roles of these MMPs, generally thought to be similar, could improve the design of therapeutic interventions aimed at controlling vascular remodeling.

Animals↗