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PubMed2005

Nanoscale topography modulates corneal epithelial cell migration.

The purpose of this study was to evaluate the effect of surface topographic features that mimic the corneal epithelial basement membrane on cell migration. We used electron-beam and X-ray lithography and reactive ion etching to pattern silicon wafers with pitches (groove width plus ridge width) of nano- and microscale dimensions (pitches ranged from 400 to 4000 nm). Additionally, polyurethane patterned surfaces were created by replication molding techniques to allow for real-time imaging of migrating cells. Individual SV40-transformed human corneal epithelial cells frequently aligned with respect to the underlying surface patterns and migrated almost exclusively along grooves and ridges of all pitches. Direction of migration of individual cells on smooth surfaces was random. In cell dispersion assays, colonies of cells migrated out from initially circular zones predominantly along grooves and ridges, although there was some migration perpendicular to the ridges. On smooth surfaces, cells migrated radially, equally in all directions, maintaining circular colony shapes. We conclude that substratum features resembling the native basement membrane modulate corneal epithelial cell migration. These findings have relevance to the maintenance of corneal homeostasis and wound healing, as well as to the evolution of strategies in tissue engineering, corneal prosthesis development, and cell culture material fabrication.

Cell Line, Transformed↗
PubMed2005

Mechanotransduction in endothelial cell migration.

The migration of endothelial cells (ECs) plays an important role in vascular remodeling and regeneration. EC migration can be regulated by different mechanisms such as chemotaxis, haptotaxis, and mechanotaxis. This review will focus on fluid shear stress-induced mechanotransduction during EC migration. EC migration and mechanotransduction can be modulated by cytoskeleton, cell surface receptors such as integrins and proteoglycans, the chemical and physical properties of extracellular matrix (ECM) and cell-cell adhesions. The shear stress applied on the luminal surface of ECs can be sensed by cell membrane and associated receptor and transmitted throughout the cell to cell-ECM adhesions and cell-cell adhesions. As a result, shear stress induces directional migration of ECs by promoting lamellipodial protrusion and the formation of focal adhesions (FAs) at the front in the flow direction and the disassembly of FAs at the rear. Persistent EC migration in the flow direction can be driven by polarized activation of signaling molecules and the positive feedback loops constituted by Rho GTPases, cytoskeleton, and FAs at the leading edge. Furthermore, shear stress-induced EC migration can overcome the haptotaxis of ECs. Given the hemodynamic environment of the vascular system, mechanotransduction during EC migration has a significant impact on vascular development, angiogenesis, and vascular wound healing.

Animals↗
PubMed1990

Differential modes of action of fibronectin and epidermal growth factor on rabbit corneal epithelial migration.

In order to clarify the roles of fibronectin (FN) and epidermal growth factor (EGF) in corneal wound healing, we cultured blocks of excised rabbit cornea for 24 hours in media containing one of these agents, then measured the length of the path of the epithelial layer that had migrated down the side of the block. Both FN and EGF stimulated epithelial migration significantly in a dose-dependent fashion. Responses to EGF involved a time lag of at least 12 hours before stimulation could be observed, but there was no lag-time for FN-stimulated migration. FN was maximally effective only if it was continuously present. In contrast, exposure to EGF for 6 hours did not stimulate epithelial migration, but exposure for 9 hours resulted in the same stimulatory effects as were observed after 24 hours' continuous exposure. Anti-FN antibody inhibited the FN- and EGF-stimulated migration of corneal epithelium. But anti-EGF antibody inhibited only EGF-stimulated migration and had no effect on FN-stimulated migration. These results indicate that, unlike FN, EGF need not be present, once the epithelial cells have recognized its signal. Furthermore, the stimulatory effect of EGF depended on FN, while that of FN was independent of EGF. The effects of EGF on migration of corneal epithelium may, therefore, be mediated by FN.

Animals↗
PubMed1992

Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration.

Cell migration is an important process in such phenomena as growth, development, and wound healing. The control of cell migration is orchestrated in part by cell surface adhesion molecules. These molecules fall into two major categories: those that bind to extracellular matrix and those that bind to adjacent cells. Here, we report on the role of a cell-cell adhesion molecule, platelet-endothelial cell adhesion molecule-1, (PECAM-1), a member of the lg superfamily, in the modulation of cell migration and cell-cell adhesion. PECAM-1 is a 120-130 kDa integral membrane protein that resides on endothelial cells and localizes at sites of cell-cell contact. Since endothelial cells express PECAM-1 constitutively, we studied the effects of PECAM-1 on cell-cell adhesion and migration in a null-cell population. Specifically, we transfected NIH/3T3 cells with the full length PECAM-1 molecule (two independent clones). Transfected cells containing only the neomycin resistance gene, cells expressing a construct coding for the extracellular domain of the molecule, and cells expressing the neu oncogene were used as controls. The PECAM-1 transfectants appeared smaller and more polygonal and tended to grow in clusters. Indirect immunofluorescence of PECAM-1 transfectants showed peripheral staining at sites of cell-cell contact, while the extracellular domain transfectants and the control cells did not. In two quantitative migration assays, the full-length PECAM-1 transfectants migrated more slowly than control cells. Thus, PECAM-1 transfected into a null cell appears to localize to sites of cell-cell contact, promote cell-cell adhesion, and diminish the rate of migration. These findings suggest a role for this cell-cell adhesion molecule in the process of endothelial cell migration.

Animals↗
PubMed1996

Mechanisms involved in eosinophil migration. Platelet-activating factor-induced chemotaxis and interleukin-5-induced chemokinesis are mediated by different signals.

Eosinophils play an important role in the pathogenesis of allergic diseases such as allergic asthma. Eosinophil migration in vitro can be divided into directed migration, or chemotaxis, and random migration, or chemokinesis. Here, we studied intracellular signals involved in eosinophil migration in vitro induced by platelet-activating factor (PAF) and interleukin-5 (IL-5), applying a Boyden chamber assay. Migration induced by PAF (10(-11)-10(-6) M) largely consisted of chemotaxis with some chemokinesis, whereas IL-5 (10(-12)-10(-8) M) induced chemokinesis only. Eosinophils were depleted from intracellular and extracellular Ca2+ to study the role of Ca2+ as a second messenger. Ca2+ depletion did not change PAF-induced chemotaxis, however, IL-5-induced chemokinesis was inhibited. Interestingly, PAF, but not IL-5, induced changes in [Ca2+]i. This rise originated mainly from internal stores. Inhibition of protein kinase A by H-89 and protein kinase C by GF 109203X had no effect on both forms of eosinophil migration. Addition of the protein kinase inhibitor staurosporine significantly inhibited IL-5-induced chemokinesis. Inhibition of tyrosine kinases by herbimycin A completely blocked IL-5-induced chemokinesis. PAF and IL-5-induced actin polymerization was studied to compare migratory responses with a migration-associated intracellular response. Ca2+ depletion significantly enhanced PAF-induced (10(-8) M) actin polymerization, whereas IL-5-induced actin polymerization was not influenced. Addition of staurosporine led to an increase in F-actin. Subsequent addition of PAF or IL-5 resulted in an additive increase in F-actin content. In summary, both forms of eosinophil migration are protein kinase A and protein kinase C independent. In contrast to PAF-induced chemotaxis, Il-5-induced chemokinesis was found to be completely Ca2+ and tyrosine kinase dependent.

Actins↗
PubMed1996

Modulation of neutrophil migration by exogenous gaseous nitric oxide.

We studied the effect of exogenous nitric oxide (NO) on migration of rabbit peritoneal neutrophils. Exogenous NO enhanced random migration of neutrophils in a concentration-dependent way. An optimally stimulatory effect was observed with 0.5 microM NO, whereas at higher NO concentrations the enhancing effect decreased again. NO caused a rapid and transient increase in intracellular guanosine-3',5'-cyclic monophosphate (cGMP) levels. The enhancing effect of NO on random migration was largely reversed by the inhibitors of cGMP accumulation, LY-83583 and methylene blue, and by the antagonists of cGMP-dependent protein kinase, 8-bromoguanosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-Br-cGMPS) and 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphorothioate (Rp-8-pCPT-cGMPS). These observations strongly suggest that the enhancement of random migration by NO is mediated by cGMP and cGMP-dependent protein kinase. The effect of NO on migration did not occur in the absence of extracellular calcium. Although NO did not induce a measurable elevation of intracellular free calcium, pre-incubation with the intracellular calcium chelator Fura-2/AM abolished the enhancing effect of NO. It appears therefore that a small change in the level of cytoplasmic free calcium does play a role in the enhancement of random migration by NO. High concentrations of NO were found to inhibit chemotaxis induced by an optimal concentration of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). This inhibitory effect was also dependent on the presence of extracellular calcium. A role for cGMP in the inhibition of fMLP-induced chemotaxis by NO is not supported by our measurements of intracellular cGMP levels. In contrast to the effects on fMLP, NO did not affect chemotaxis induced by the phorbol ester PMA. In conclusion, we show that NO, not derived from NO donors but applied directly, may stimulate or inhibit neutrophil migration, dependent on the concentration. The enhancing effect of NO on random migration is mediated by cGMP, which emphasizes the importance of this second messenger as a modulator of neutrophil functional.

Aminoquinolines↗
PubMed2000

Migration of dendritic cells within 3-D collagen lattices is dependent on tissue origin, state of maturation, and matrix structure and is maintained by proinflammatory cytokines.

The function of dendritic cells (DC) depends on active migration through three-dimensional (3-D) extracellular matrices. We have analyzed the migration of murine DC from different tissue origins within 3-D collagen lattices through the use of time-lapse videomicroscopy and single-cell tracking. Directly after incorporation, 50-90% of DC from the spleen (spDC) and Langerhans cells freshly isolated from the epidermis (fLC) displayed active motility in these matrices. Whereas mature spDC showed multilateral pseudopod dynamics as well as fast and heterogeneous migration, immature fLC displayed a spherical shape with faint membrane processes and very homogenous, slow migration characteristics. In the absence of external stimuli, migration of both, spDC and fLC, vanished after >36 h due to cell death. Maintaining fLC viability by external granulocyte-macrophage colony-stimulating factor or tumor necrosis factor alpha prolonged migration up to 5 days. During this period fLC transformed into mature cells with large dendrites, thereby developing a heterogeneous migration pattern more similar to spDC. In randomly polymerized collagen matrices cell paths were without preferential orientation. In contrast, in artificially aligned lattices directional paths in accordance with the forced fiber orientation were observed. Thus, migration is an inherent property of DC, largely influenced by tissue origin, degree of maturity, and the 3-D structure of the environment.

Animals↗
PubMed2003

Cellular migration in the postnatal rat cerebellar cortex: confocal-infrared microscopy and the rapid Golgi method.

Confocal laser microscopy of DiI-labeled slices of postnatal rat cerebellum (postnatal Day 4-10; P4-10) was compared to infrared microscopy and the rapid Golgi method (P0-14) to investigate postnatal migration of granule neurons. Vertical migration of the granule neurons occurred already at birth (P0). Surprisingly, mossy fibers often reached the external granule cell layer and were in close contact with the external granule cells. These mossy fibers may play a role in initiating granule cell migration. At this age, cell bodies of the immature neurons were attached to the external basal lamina by a process and extended down toward the presumptive internal granule cell layer. At P14, some granule cells remained attached to the surface, although their cell bodies exhibited the typical morphology of mature granule neurons and were located deep in the internal granule cell layer. These cells extended their endfeet-like processes all the way to the surface of the brain. These results indicate that the vertical pathways of granule cell migration form early and persist throughout the period of granule cell migration. Confocal infrared microscopy of DiI-labeled sections and the rapid Golgi method also allowed demonstration of tangentially migrating neurons that made one or more turns on the way to the internal granule cell layer. The rapid Golgi method confirmed that many Bergmann glial processes end at the level of the tangentially migrating granule cells whereas others project to the surface. These observations show that migratory granule cells take several different routes to their final destination, which cannot be explained by so-called radial glial guidance. The only mode of migration in evidence is consistent with process elongation and translocation of the nucleus within the preformed processes.

Animals↗
PubMed2001

Unique neuronal tracers show migration and differentiation of SVZ progenitors in organotypic slices.

Continual neurogenesis in the subventricular zone (SVZ) of postnatal and adult mammalian forebrain has been well documented, but the mechanisms underlying cell migration and differentiation in this region are poorly understood. We have developed novel in vivo and in vitro methods to investigate these processes. Using stereotaxic injections of a variety of tracers/tracker [Cholera Toxin beta subunit (CTb-), Fluorogold (FG), and Cell Tracker Green (CTG)], we could efficiently label SVZ cells. Over several days, labeled cells migrate along the rostral migratory stream (RMS) to their final differentiation site in the olfactory bulb (OB). The compatibility of these tracers/trackers with immunohistochemistry allows for cell labeling with multiple dyes (e.g., CTb and CTG) and/or specific cell antigens. To investigate the dynamics of migration we labeled SVZ progenitor cells with small injections of CTG and monitored the movements of individual cells in fresh parasagittal brain slices over several hours using time-lapse confocal microscopy. Our observations suggest that tangential cell migration along the RMS occurs more rapidly than radial cell migration into the OB granule cell layer. To investigate migration over longer time periods, we developed an in vitro organotypic slice in which labeled SVZ progenitors migrate along the RMS and differentiate within the OB. The phenotypic characteristics of these cells in vitro were equivalent to those observed in vivo. Taken together, these methods provide useful tools investigating cell migration and differentiation in a preparation that maintains the anatomical organization of the RMS.

Animals↗
PubMed2001

Reactive oxygen and NF-kappaB in VEGF-induced migration of human vascular smooth muscle cells.

Migration and proliferation of vascular smooth muscle cells (VSMC) contribute to angiogenesis and the lesions of atherosclerosis. Since, vascular endothelial growth factor (VEGF) is overexpressed by VSMC in intima of atherosclerotic human coronary arteries, we determined if VEGF could stimulate VSMC migration and the intracellular signals involved. VEGF induced VSMC migration but had no significant activity on proliferation. VEGF increased intracellular reactive oxygen species (ROS), NF-kappaB activation and IL-6 expression. Blockade of the generation of intracellular ROS by antioxidants inhibited VEGF-induced NF-kappaB activation, IL-6 expression, and cell migration indicating that generation of ROS was required for NF-kappaB activation and the chemotactic activity of VEGF. Expression of a mutated, nondegradable form of inhibitor of NF-kappaB (IkappaB-alphaM) suppressed VEGF-triggered activation of NF-kappaB and upregulation of IL-6 as well as VSMC migration. Neutralization of IL-6 by its antibody significantly attenuated the migration stimulated by VEGF. Collectively, our data provide the first evidence that intracellular ROS and NF-kappaB are required for VEGF-mediated smooth muscle cell migration. Further, IL-6 induced by VEGF is involved in the ability of the growth factor to stimulate migration.

Antioxidants↗
PubMed1999

Migratory phenotypes of HSC-3 squamous carcinoma cell line induced by EGF and PMA: relevance to migration of loosening of adhesion and vinculin-associated focal contacts with prominent filopodia.

Cell migration is involved in carcinoma cell invasion and wound healing. We examined motogenic cytokines that potentiated migration of human HSC-3 carcinoma cells. To assess migratory activity, modified Boyden chambers were used. Among a variety of potential motogenic cytokines, epidermal growth factor (EGF) enhanced migration of HSC-3 cells both on collagen and fibronectin. Phorbol myristate acetate (PMA) also enhanced migration. Inhibitors of protein kinase C completely inhibited PMA-induced migration, but only partly inhibited EGF-induced migration. Protein kinase A was also involved in the EGF-induced signaling pathway for migration. Although the signaling pathways were independent, and the cell shape on collagen was different from that on fibronectin, migratory cells stimulated by EGF or PMA showed common morphology on different ligands. The cells were polygonal or round in shape and the loss of long cytoplasmic extensions was noted. Migratory HSC-3 cells stimulated by EGF or PMA became less adhesive to collagen and fibronectin. Since both EGF- and PMA-stimulated migration did not require de novo protein synthesis, the signaling pathways possibly lead to assembly and disassembly of an actin cytoskeleton. Immunofluorescence for vinculin was concentrated into focal contacts in EGF- and PMA-stimulated HSC-3 cells, whereas the fluorescence signal was hardly detected in non-stimulated cells. Talin and beta1 integrin were immunolocalized at focal contacts in non-stimulated cells, and it remained unchanged in stimulated cells. Numerous filopodia visualized with actin immunofluorescence were formed around stimulated HSC-3 cells, whereas filopodia were short and sparse around elongated cytoplasms in non-stimulated cells. Thus, shortening of cytoplasmic extensions with numerous filopodia, loosening of adhesion, and vinculin-associated focal contacts were regarded as migratory phenotypes.

Carcinogens↗
PubMed1993

Pronuclear positioning and migration during fertilization in Pelvetia.

The position and migration of egg and sperm pronuclei were studied in the brown alga Pelvetia. The egg pronucleus was located near the center of the cell before and after fertilization and, unlike pronuclei in animal eggs, did not migrate. Inhibitor studies indicated that anchoring of the egg pronucleus in the cell center was dependent on microtubules and microfilaments. An extensive array of microtubules, many of which extended into the actin-rich egg cortex, was associated with the egg pronucleus. Migration of the sperm pronucleus was investigated quantitatively in both living and fixed zygotes. Migration occurred linearly at rates from 0.11 to 0.29 microns/min and was oriented directly toward the egg pronucleus in the cell center. Sperm penetration was inhibited by cytochalasin D, which disrupts F-actin function, whereas sperm pronuclear migration was sensitive to the microtubule-depolymerizing drug, nocodazole. Microtubules associated with the migrating sperm pronucleus formed a sperm trail that terminated at the egg cortex. As these were the only microtubules associated with the sperm at early stages of migration, we conclude that they provide the force for migration.

Cell Nucleus↗
PubMed1993

Three populations of migrating amphibian embryonic cells utilize different guidance cues.

Previous investigations designed to identify the molecule(s) governing the directed migration of the amphibian pronephric duct (PND) revealed a requirement for a glycosyl phosphatidylinositol (GPI)-linked cell surface molecule, possibly the ectoenzyme alkaline phosphatase (AP). Cranial neural crest cells (CNC) grafted to the flank migrate along the same pathways as the PND, suggesting that PND and CNC guidance systems might have a common molecular basis. Both PND and CNC migration pathways display AP. The present experiments demonstrate, however, that GPI-linked molecules on these pathways are not required for migration of either cell type. Because PND cells themselves express AP prominently but CNC cells do not, we asked whether the GPI-linked molecule required for PND migration resides on the PND cells themselves. Treatment of PND cells with phosphatidylinositol-specific phospholipase C, an enzyme that removes GPI-linked proteins, prevents their migration. Transplantation experiments show that although CNC cells are capable of following PND migration pathways, the converse is not the case. Extension of the transplantation experiments to include trunk neural crest (TNC) cells indicates that although CNC cells can follow PND guidance information on the flank, PND, CNC, and TNC cells all normally utilize different molecular cues to guide their migrations in situ.

Ambystoma↗
PubMed1993

Cell adhesion molecules and the migration of LHRH neurons during development.

During embryogenesis, LHRH neurons arise in the olfactory epithelium, migrate along the olfactory nerve, and enter the forebrain. We have examined the distribution of several cell adhesion molecules (CAMs) in the developing chick olfactory system and brain to determine whether differential distributions of these adhesion molecules might be important in pathway choices made by migrating LHRH neurons. Single- and double-label immunocytochemical studies indicated that high levels of N-CAM and N-cadherin were expressed throughout the olfactory epithelium and not restricted to the medial half of the olfactory epithelium where most of the LHRH neurons originate. Further, high levels of N-CAM, Ng-CAM, and N-cadherin were uniformly expressed throughout the entire olfactory nerve while migrating LHRH neurons were confined to the medial half of the nerve. However, once LHRH neurons reach the brain, they migrate dorsally and caudally, tangential to the medial surface of the forebrain, along a region enriched in N-CAM and Ng-CAM. After this first stage of migration within the brain, LHRH neurons migrate laterally. At this stage, there is no correlation between the intensity of N-CAM and Ng-CAM immunostaining and the location of LHRH neurons. These results suggest that N-CAM, Ng-CAM, and N-cadherin do not play a guiding role in LHRH neuronal migration through the olfactory epithelium and olfactory nerve but that migrating LHRH neurons may follow a "CAM-trail" of N-CAM and Ng-CAM along the medial surface of the forebrain.

Animals↗
PubMed2001

Analysis of melanocyte precursors in Nf1 mutants reveals that MGF/KIT signaling promotes directed cell migration independent of its function in cell survival.

Neural crest-derived melanocyte precursors (MPs) in avian and murine embryos emerge from the dorsal neural tube into a migration staging area (MSA). MPs subsequently migrate from the MSA on a dorsolateral pathway between the dermamyotome and the overlying epithelium. In mouse embryos, MPs express the receptor tyrosine kinase, KIT, and require its cognate ligand, Mast cell growth factor (MGF), for survival and differentiation. Prior to the onset of MP migration, MGF is expressed on the dorsolateral pathway at some distance from cells in the MSA and appears to be required for normal MP development. To learn if MGF is required solely for MP survival on this pathway, or if it also provides directional cues for migration, we uncoupled survival from chemoattractive or motogenic functions of this ligand using mice that carry a targeted mutation at the Neurofibromin (Nf1) locus and consequently lack RAS-GAP function. We show that Nf1-mutant MPs survive in the absence of MGF in vitro and in vivo and that Nf1-mutant MPs disperse normally on the lateral migration pathway in the presence of MGF. In contrast, Nf1-mutant MPs persist in the location of the MSA but are not observed on the lateral migration pathway in double-mutant mice that also lack MGF. We conclude that MGF/KIT function provides a signal required for directed migration of the MPs on the lateral pathway in vivo, independent of its function in survival. We further suggest that the MGF mediates MP migration through a signaling pathway that does not involve RAS.

Animals↗
PubMed2001

Time-lapse analysis of living mouse germ cell migration.

In mouse embryos, the primordial germ cells arise during gastrulation prior to, and distant from, the prospective gonads. Observations of PGCs in culture, and in fixed sections, have suggested, but not proved, that they migrate to the gonad by a process of active migration. The opaque nature of the early mouse embryo has precluded direct observation. Using confocal microscopy, we have filmed living PGCs expressing eGFP in tissue slices from mouse embryos at different stages of development. We find four clearly distinct phases of PGC migration. First, until E9.0-E9.5, PGCs are already highly motile, but do not leave the gut. Second, in the E9.0-E9.5 period, before the mesentery forms, PGCs very rapidly exit the gut, but do not migrate towards the genital ridges. Third, during the E10.0-E10.5 period, PGCs migrate directionally from the dorsal body wall into the genital ridges. In contrast to the prevailing model of germ cell migration, very few, if any, PGCs found in the gut mesentery at E10.5 migrate into the genital ridges. Finally, at E11.5, PGCs are slowing and the direction of movement is dependent on the sex of the embryo. This allows, for the first time, a formal description of the events of PGC migration in the mouse.

Animals↗
PubMed1995

Functional role of cell surface integrins on human trophoblast cell migration: regulation by TGF-beta, IGF-II, and IGFBP-1.

Trophoblast invasion of the human uterus is stringently controlled by the microenvironment. Invasive extravillous trophoblast cells in situ as well as in culture express a selective repertoire of cell surface integrins. Since migration is a necessary step in the invasion cascade, we tested whether certain integrins or invasion-regulating molecules, i.e., TGF-beta, IGF-II, and IGFBP-1 produced at the fetomaternal interface had a functional role on trophoblast migration. Flow cytometric analysis of integrin expression and the use of an in vitro cell migration assay revealed that exogenous TGF-beta upregulates integrin expression and reduces migratory ability to the invasive trophoblast, whereas IGF-II has no effect on integrin expression but stimulates migration. Trophoblast migration was inhibited in the presence of alpha 5 and beta 1 integrin blocking antibodies, indicating its dependence on the expression of these subunits. Furthermore, IGFBP-1, which contains an RGD sequence recognizing certain integrins, stimulated migration, an effect that was blocked by pretreatment with anti-alpha 5 or -beta 1 blocking Abs. These studies demonstrate that the migration of first trimester invasive trophoblast in vitro (1) requires the expression of alpha 5 and beta 1 integrin subunits, (2) is inhibited by TGF-beta, possibly due to increased cell adhesiveness to the extracellular matrix, (3) is stimulated by IGF-II by an as yet undetermined mechanism, and (4) is stimulated by IGFBP-1, likely by interaction with the RGD binding site of the alpha 5 beta 1 integrin. The invasion-regulating effects of TGF-beta, IGF-II, and IGFBP-1 may thus, at least in part, be due to their migration-regulating effects on the invasive trophoblast.

Antibodies↗
PubMed1999

Role of epidermal growth factor receptor in basal and stimulated colonic epithelial cell migration in vitro.

Colonic mucosal wounds are repaired, in part, by epithelial migration. Signaling mechanisms regulating this migration are poorly characterized. This study aimed to examine the role that the epidermal growth factor (EGF) receptor (EGF-R) and its ligands, EGF and transforming growth factor-alpha (TGF-alpha), play in migration in wounded in vitro models of colonic epithelium. Migration was assessed over 24 h in circular wounds made in confluent monolayers of LIM1215 human colon cancer cells. EGF and TGF-alpha stimulated migration twofold from 4 h after wounding. Basal migration and the motogenic effects of short chain fatty acids and hepatocyte growth factor were mediated through enhanced binding of TGF-alpha to EGF-R, while trefoil peptide-mediated motogenesis required EGF-R activation independently of TGF-alpha binding. Activation of protein kinase C (PKC) stimulated migration, an effect more potent than, and independent of, EGF-R activation. However, neither inhibition of PKC by Ro 31-8220 nor depletion of PKC by pretreatement with phorbol myristate acetate attenuated EGF-R-mediated motogenesis. In conclusion, EGF-R activation via TGF-alpha binding, or intracellularly, mediates basal LIM1215 migration and the effects of several motogens, with the exception of PKC activators. Since EGF-R and PKC have physiological activators in vivo, they may control colonic mucosal repair processes following injury.

Acetates↗