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PubMed2005

Immunohistochemical localization of beta1 and beta4 integrins in mouse endometrium during implantation and early pregnancy.

Implantation presents the remarkable synchronisation between the development of embryo and differentiation of endometrium. Cell-cell adhesion is an important phenomenon taking place during blastocyst implantation in uterine membrane. We think that the investigation of existence and the level of integrins in women can be a guide for treatment of infertility. Our purpose in this study was to show expression beta1 and beta4 integrins on gestational days 4, 6, 12 by immunohistochemical methods and to investigate whether beta4 integrin is a useful marker for receptivity. beta1 and beta4 integrin were exhibited on surface epithelium on gestational day 4. On the other hand, strong beta4 immunoreactivity was detected on surface epithelium and glandular cells on gestational day 12 but no beta1 reactivity was present in the surface epithelium and glandular cells on day 12. In conclusion, both beta1 and beta4 integrins may have a role in implantation process because positive immunoreactivity was seen on apical membrane of surface epithelium on day 4 when implantation occurred. The localization to apical pole of surface epithelium suggest a role for beta1, beta4 integrins in initial embryo and endometrium interaction. It does not seem that beta1 integrin has a role supporting pregnancy since expression of beta4 on surface epithelium and glandular epithelium disappeared on day 12. beta4 integrin expression increasing on day 12 of pregnancy leads us to think a possible functional role supporting pregnancy.

Animals↗
PubMed2002

ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin.

ADAM15 belongs to the family of proteins containing disintegrin and metalloprotease domains (ADAM) that have been implicated in cell adhesion via integrin binding and shedding of cell surface molecules. Here we provide the first report on the localization of an ADAM in adherens junctions. We show that ADAM15 colocalizes with a cell adhesion molecule, vascular endothelial (VE)-cadherin, which mediates endothelial cell adherens junction formation. In contrast, the distribution of ADAM15 correlates poorly with the localization in cell contacts of one of its proposed ligands, the beta1-integrin. Furthermore, ADAM15 accumulation in cell-cell contacts is preceded by VE-cadherin-mediated adherens junction formation. To investigate the dependence of ADAM15 surface expression on adherens junction formation, we coexpressed VE-cadherin with ADAM15 and an ADAM15 green fluorescence protein (GFP) fusion protein in Chinese hamster ovary cells. VE-cadherin coexpression results in the translocation of ADAM15-GFP to the cell periphery. Analysis of cell surface levels of ADAM15 and ADAM15-GFP, with or without VE-cadherin coexpression, clearly demonstrates that VE-cadherin can drive surface expression of ADAM15. Our data suggest that ADAM15 may be a novel component of adherens junctions and thus could play a role in endothelial functions that are mediated by these cell contacts.

ADAM Proteins↗
PubMed2006

Vimentin function in lymphocyte adhesion and transcellular migration.

Although the adhesive interactions of leukocytes with endothelial cells are well understood, little is known about the detailed mechanisms underlying the actual migration of leukocytes across the endothelium (diapedesis). Leukocytes have been shown to use both paracellular and transcellular routes for transendothelial migration. Here we show that peripheral blood mononuclear cells (PBMCs; T- and B-lymphocytes) preferentially use the transcellular route. The intermediate filaments of both endothelial cells and lymphocytes formed a highly dynamic anchoring structure at the site of contact between these two cell types. The initiation of this process was markedly reduced in vimentin-deficient (vim(-/-)) PBMCs and endothelial cells. When compared with wild-type PBMCs, vim(-/-) PBMCs showed a markedly reduced capacity to home to mesenteric lymph nodes and spleen. Furthermore, endothelial integrity was compromised in vim(-/-) mice, demonstrating that intermediate filaments also regulate the barrier that governs leukocyte extravasation. Absence of vimentin resulted in highly aberrant expression and distribution of surface molecules critical for homing (ICAM-1 and VCAM-1 on endothelial cells and integrin-beta1 on PBMCs). These data show that intermediate filaments are active in lymphocyte adhesion and transmigration.

Animals↗
PubMed2000

Human bone cell hyperpolarization response to cyclical mechanical strain is mediated by an interleukin-1beta autocrine/paracrine loop.

Mechanical stimuli imparted by stretch, pressure, tension, fluid flow, and shear stress result in a variety of biochemical responses important in bone (re)modeling. The molecules involved in the recognition and transduction of mechanical stimuli that lead to modulation of bone cell function are not yet fully characterized. Cyclical pressure-induced strain (PIS) induces a rapid change in membrane potential of human bone cells (HBC) because of opening of membrane ion channels. This response is mediated via integrins and requires tyrosine kinase activity and an intact actin cytoskeleton. We have used this electrophysiological response to further study the signaling events occurring early after mechanical stimulation of HBC. Stimulation of HBC at 0.33 Hz PIS, but not 0.104 Hz PIS, results in the production of a transferable factor that induces membrane hyperpolarization of unstimulated HBC. The production of this factor is inhibited by antibodies to beta1-integrin. Interleukin-1beta (IL-1beta and prostaglandin E2 (PGE2) were identified as candidate molecules for the transferable factor as both were shown to induce HBC hyperpolarization by opening of small conductance calcium-activated potassium channels, the means by which 0.33 Hz PIS causes HBC hyperpolarization. Antibodies to IL-1beta, but not other cytokines studied, inhibit the hyperpolarization response of HBC to 0.33 Hz PIS. Comparison of the signaling pathways required for 0.33 Hz PIS and IL-1beta-induced membrane hyperpolarization shows that both involve the phospholipase C/inositol triphosphate pathway, protein kinase C (PKC), and prostaglandin synthesis. Unlike 0.33 Hz PIS-induced membrane hyperpolarization, IL-1beta-induced hyperpolarization does not require tyrosine kinase activity or an intact actin cytoskeleton. These studies suggest that 0.33 Hz PIS of HBC induces a rapid, integrin-mediated, release of IL-1beta with a subsequent autocrine/paracrine loop resulting in membrane hyperpolarization. IL-1beta production in response to mechanical stimuli is potentially of importance in regulation of bone (re)modeling.

Antibodies↗
PubMed2002

Effect of growth factor-fibronectin matrix interaction on rat type II cell adhesion and DNA synthesis.

Type II cells attach, migrate, and proliferate on a provisional fibronectin-rich matrix during alveolar wall repair after lung injury. The combination of cell-substratum interactions via integrin receptors and exposure to local growth factors are likely to initiate the signals required for cell proliferation, differentiation, reepithelialization, and ultimate restoration of the alveolar wall structure. Accordingly, primary cultured type II cells have been shown to bind fibronectin, in part through the alpha5beta1 integrin, and to respond to growth factors that induce type II cell proliferation, such as fibroblast growth factor 1 (FGF-1). The purpose of this study was to determine whether or not FGF-1 modifies type II cell attachment to fibronectin, and if together they affect DNA synthesis. Attachment assays showed that FGF-1 treatment enhanced type II cell adhesion to fibronectin. This effect correlated with an increase in beta1 integrin cell surface expression, and with the formation of cytoskeletal stabilizing structures such as lamellipodial extensions and stress fibers. FGF-1 also induced an increase in thymidine incorporation into DNA. Together FGF-1 and fibronectin appear to promote adhesion, cytoskeletal organization, and increased DNA synthesis, and in this way influence cell-substratum interactions and signaling during alveolar repair.

Actins↗
PubMed2003

Role of integrin-linked kinase in nerve growth factor-stimulated neurite outgrowth.

The role of integrin-linked kinase (ILK), a kinase that is involved in various cellular processes, including adhesion and migration, has not been studied in primary neurons. Using mRNA dot blot and Western blot analysis of ILK in rat and human brain tissue, we found that ILK is expressed in various regions of the CNS. Immunohistochemical and immunocytochemical techniques revealed granular ILK staining that is enriched in neurons and colocalizes with the beta1 integrin subunit. The role of ILK in neurite growth promotion by NGF was studied in rat pheochromocytoma cells and dorsal root ganglion neurons using a pharmacological inhibitor of ILK (KP-392) or after overexpression of dominant-negative ILK (ILK-DN). Both molecular and pharmacological inhibition of ILK activity significantly reduced NGF-induced neurite outgrowth. Survival assays indicate that KP-392-induced suppression of neurite outgrowth occurred in the absence of cell death. ILK kinase activity was stimulated by NGF. NGF-mediated stimulation of phosphorylation of both AKT and the Tau kinase glycogen synthase kinase-3 (GSK-3) was inhibited in the presence of KP-392 and after overexpression of ILK-DN. Consequently, ILK inhibition resulted in an increase in the hyperphosphorylation of Tau, a substrate of GSK-3. Together these findings indicate that ILK is an important effector in NGF-mediated neurite outgrowth.

Animals↗
PubMed2006

Crucial role of fibroblast integrins alpha2 and beta1 in maintaining the structural and mechanical properties of the skin.

BACKGROUND: In vivo functions of integrins in dermis have been investigated using several types of genetically integrin deficient mice. However, there are few studies to clarify actual in vivo functions of integrins in the dermis using normal type animals. OBJECTIVE: We investigated the actual in vivo functions of integrins in maintaining structural and mechanical properties in the normal skin by means of blocking interactions between fibroblasts and the extracellular matrix (ECM). METHODS: Intradermal injection of anti-integrin alpha2 or beta1 antibody into hairless rat skin was used to block the function of integrins. The dermal thickness was measured by an ultrasound scanner and the elastic properties of the skin was measured by Cutometer. RESULTS: Blocking integrin alpha2 or beta1 alone caused a moderate increase in dermal thickness. Blocking of integrins alpha1, alphaL or beta2 alone or blocking both integrins alpha1 and beta1 did not cause any change in the skin. However, blocking of both integrins alpha2 and beta1 caused a significant increase in dermal thickness accompanied by a marked loss of elastic properties. A clear change of the skin was observed within several minutes after injection, and continued for several hours. Treatment of human skin fibroblasts in collagen gel lattices with a mixture of anti-integrin alpha2 and beta1 antibodies in vitro caused marked and rapid morphological changes, but significant change was not observed with a treatment of alpha1, alpha2 or beta1 antibody alone. CONCLUSION: These results indicate that simultaneous functioning of integrins alpha2 and beta1 in fibroblasts play a crucial role in maintaining the structural and mechanical properties in the skin, which suggests that fibroblasts actively regulate collagen networks via these integrins.

Animals↗
PubMed2002

Merosin-integrin promotion of skeletal myofiber cell survival: Differentiation state-distinct involvement of p60Fyn tyrosine kinase and p38alpha stress-activated MAP kinase.

Myofiber survival and suppression of anoikis depend in large part on the merosin (laminin-2/-4)-integrin alpha7beta1D cell adhesion system; however, the question remains as to the nature of the signaling molecules/pathways involved. In the present study, we investigated this question using the C2C12 cell model of myogenic differentiation and its merosin- and laminin-deficient derivatives. Herein, we report that: 1) of four members of the Src family of tyrosine kinases studied (p60Src, p53/56Lyn, p59Yes, or p60Fyn), the expression and activity of p60Fyn are found in myotubes exclusively; 2) a severe decrease of p60Fyn activity correlates with myotube apoptosis/anoikis induced by pharmocological compounds (herbimycin A or PP2) which inhibit tyrosine kinases of the Src family, by merosin deficiency and by beta1 integrin inhibition; 3) myoblast survival depends on Fak and the MEK/Erk pathway, in contrast to myotubes; 4) the PI3-K pathway is not involved in either myoblast or myotube survival; and 5) p38alpha SAPK stimulation and activity (but not that of p38beta) are required in the progression of myotube apoptosis/anoikis induced by p60Fyn inhibition, merosin deficiency or beta1 integrin-inhibition; however, p38 is not involved in myoblast apoptosis. Taken together, these results suggest that the promotion of myotube survival by the merosin-alpha7beta1D adhesion system involves p60Fyn, and that disruptions in this cell adhesion system induce myotube apoptosis/anoikis through a p38alpha SAPK-dependent pathway.

Animals↗
PubMed2006

Sialilated beta1,6 branched N-oligosaccharides modulate adhesion, chemotaxis and motility of melanoma cells: Effect on invasion and spontaneous metastasis properties.

B16BL6 cells, selected specifically for invasive characteristics from B16F10 mouse melanoma cells, displayed greater ability to metastasize to lungs and produced larger colonies than the parent cells, when injected intravenously. When the two cell lines were compared for surface beta1,6-branched N-oligosaccharides by flow cytometry using Leuco-Phyto-Heam-Agglutinin, B16BL6 were found to express significantly higher levels. Inhibition of the oligosaccharide expression, by treatment of the cells with swainsonine or antisense-N-acetyl glucosaminyl-transferase-V, significantly reduced metastasis and invasion (>50%). Further, inhibition of oligosaccharides on the molecules like beta1 integrin (one of the major carriers) caused 30-45% reduction in their adherence to extra-cellular-matrix components especially collagen IV and laminin, and chemotaxis towards fibronectin and matrigel. The inhibition also decreased haptotaxis by approximately 50% to fibronectin but surprisingly was enhanced towards laminin by approximately 75%. The cells on which the expression of these oligosaccharides was inhibited failed to exhibit the characteristic spontaneous metastasis and adhesion properties of B16BL6 cells. In none of the cases, however, the secretion of matrix-metallo-proteases correlated with oligosaccharide expression. Sialylation of surface oligosaccharides was found to be accompanied by even higher motility and adherence to the substrates. These results strongly support an important role of cell surface beta1,6-linked N-oligosaccharides, especially the sialylated derivatives, in the processes that influence invasion and metastasis.

Animals↗
PubMed1999

Soluble collagen VI induces tyrosine phosphorylation of paxillin and focal adhesion kinase and activates the MAP kinase erk2 in fibroblasts.

Signals from the extracellular matrix can modulate cellular differentiation and gene expression. We have shown previously that in contrast to other extracellular matrix molecules pepsin-solubilized collagen VI (CVI) can stimulate DNA synthesis of various mesenchymal cell types, apparently independent of integrin-mediated signal transduction. In order to further elucidate collagen VI-induced signaling events, we exposed mouse 3T3 fibroblasts and human HT1080 fibrosarcoma cells to soluble CVI. CVI induced tyrosine phosphorylation of proteins that associate with focal adhesions, such as paxillin, focal adhesion kinase (FAK), and p130CAS. Furthermore, it activated the mitogen-activated protein kinase, erk2. Kinetic analysis showed that these phosphorylations were transient, reaching a maximum after 5 min for transformed HT1080 cells and 30 min for 3T3 fibroblasts. These effects were partly inhibited by a beta1-integrin function blocking antibody and by single chains of CVI. Our results indicate that soluble fragments of native collagen VI, a ubiquitous component of the interstitial extracellular matrix, can mediate stimulation of DNA synthesis via tyrosine phosphorylation of paxillin, FAK, p130CAS, and erk2 in the absence of classical growth factors. Thus, CVI may serve as a matrix-derived sensor that allows for rapid reconstitution of a tissue defect by activating nearby mesenchymal cells.

3T3 Cells↗
PubMed2000

Ephrin-A5 modulates cell adhesion and morphology in an integrin-dependent manner.

The ephrins are membrane-tethered ligands for the Eph receptor tyrosine kinases, which play important roles in patterning of the nervous and vascular systems. It is now clear that ephrins are more than just ligands and can also act as signalling-competent receptors, participating in bidirectional signalling. We have recently shown that ephrin-A5 signals within caveola-like domains of the plasma membrane upon engagement with its cognate Eph receptor, leading to increased adhesion of the cells to fibronectin. Here we show that ephrin-A5 controls sequential biological events that are consistent with its role in neuronal guidance. Activation of ephrin-A5 induces an initial change in cell adhesion followed by changes in cell morphology. Both effects are dependent on the activation of beta1 integrin involving members of the Src family of protein tyrosine kinases. The prolonged activation of ERK-1 and ERK-2 is required for the change in cell morphology. Our work suggests a new role for class A ephrins in specifying the affinity of the cells towards various extracellular substrates by regulating integrin function.

3T3 Cells↗
PubMed2006

Phenotypic drift in human tenocyte culture.

Tendon ruptures are increasingly common, repair can be difficult, and healing is poorly understood. Tissue engineering approaches often require expansion of cell numbers to populate a construct, and maintenance of cell phenotype is essential for tissue regeneration. Here, we characterize the phenotype of human Achilles tenocytes and assess how this is affected by passaging. Tenocytes, isolated from tendon samples from 6 patients receiving surgery for rupture of the Achilles tendon, were passaged 8 times. Proliferation rates and cell morphology were recorded at passages 1, 4, and 8. Total collagen, the ratio of collagen types I and III, and decorin were used as indicators of matrix formation, and expression of the integrin beta1 subunit as a marker of cell-matrix interactions. With increasing passage number, cells became more rounded, were more widely spaced at confluence, and confluent cell density declined from 18,700/cm2 to 16,100/cm2 ( p = 0.009). No change to total cell layer collagen was observed but the ratio of type III to type I collagen increased from 0.60 at passage 1 to 0.89 at passage 8 ( p < 0.001). Decorin expression significantly decreased with passage number, from 22.9 +/- 3.1 ng/ng of DNA at passage 1, to 9.1 +/- 1.8 ng/ng of DNA at passage 8 ( p < 0.001). Integrin expression did not change. We conclude that the phenotype of tenocytes in culture rapidly drifts with progressive passage.

Achilles Tendon↗
PubMed1999

Synergism among lysophosphatidic acid, beta1A integrins, and epidermal growth factor or platelet-derived growth factor in mediation of cell migration.

GD25 cells lacking the beta1 integrin subunit or expressing beta1A with certain cytoplasmic mutations have poor directed cell migration to platelet-derived growth factor (PDGF) or epidermal growth factor (EGF), ligands of receptor tyrosine kinases, or to lysophosphatidic acid (LPA), a ligand of G-protein-coupled receptors (Sakai, T., Zhang, Q., Fässler, R., and Mosher, D. F. (1998) J. Cell Biol. 141, 527-538 and Sakai, T., Peyruchaud, O., Fässler, R., and Mosher, D. F. (1998) J. Biol. Chem. 273, 19378-19382). We demonstrate here that LPA synergizes with signals induced by beta1A integrins and ligated EGF or PDGF receptors to modulate migration. When LPA was mixed with EGF or PDGF, migration was greater than with EGF or PDGF alone. The enhancement was greater for beta1A-expressing cells than for beta1-null cells. Cells expressing beta1A with mutations of prolines or tyrosines in conserved cytoplasmic NPXY motifs had blunted migratory responses to mixtures of LPA and EGF or PDGF. The major effects on beta1A-expressing cells of LPA when combined with EGF or PDGF were to sensitize cells so that maximal responses were obtained with >10-fold lower concentrations of growth factor and increase the chemokinetic component of migration. Sensitization by LPA was lost when cells were preincubated with pertussis toxin or C3 exotransferase. There was no evidence for transactivation or sensitization of receptors for EGF or PDGF by LPA. EGF or PDGF and LPA caused activation of mitogen-activated protein kinase by pertussis toxin-insensitive and -sensitive pathways respectively, but activation was not additive. These findings indicate that signaling pathways initiated by the cytoplasmic domains of ligated beta1A integrins and tyrosine kinase receptors interact with signaling pathways initiated by LPA to facilitate directed cell migration.

ADP Ribose Transferases↗
PubMed1999

Alterations in focal adhesion kinase activity and associated proteins during malignant conversion of mouse keratinocytes.

Focal adhesion kinase (pp125FAK) has well-established functions in the attachment and growth of cells in culture and has been implicated as a marker of malignant progression in human tumors. To evaluate its role in the metastatic conversion of mouse skin tumors, pp125FAK activity and protein expression were examined in normal and transformed keratinocyte cell lines. Malignant mouse keratinocyte lines exhibited a reproducible increase in the specific activity of pp125FAK compared with that of nontransformed control cells. An increase in pp125FAK activity was not observed in papilloma-derived keratinocytes, indicating that this response correlated with malignant progression of cells and not cell transformation per se. Immune complex kinase assays and metabolic labeling with [32P]orthophosphate also revealed the specific loss of pp125FAK-associated proteins in the metastatic keratinocytes. Furthermore, immunocytochemical examination revealed an altered distribution of pp125FAK in the cells with malignant potential compared with normal and papilloma-inducing keratinocytes. The cells with malignant potential also exhibited reduced levels of paxillin and integrin beta1 as well as altered distribution of paxillin, reinforcing the notion that specific changes in the composition of focal adhesions contribute to the malignant conversion of mouse keratinocytes.

Animals↗
PubMed2004

Activation of epidermal growth factor receptor causes astrocytes to form cribriform structures.

Epidermal growth factor receptor (EGFR) is expressed in reactive astrocytes following injury in the CNS. However, the effects of activation of the EGFR pathway in astrocytes are not well established. In the present study, we demonstrate that activation of EGFR causes optic nerve astrocytes, as well as brain astrocytes, to form cribriform structures with cavernous spaces. Formation of the cribriform structures is dependent on new protein synthesis and cell proliferation. Platelet-derived growth factor and basic fibroblast growth factor were not effective. Smooth muscle cells and epithelial cells do not form cribriform structures in response to EGFR activation. The formation of the cribriform structures appears to be related to a guided migration of astrocytes and the expression of integrin beta1 and extracellular fibronectin in response to activation of EGFR. The EGFR pathway may be a specific, signal transduction pathway that regulates reactive astrocytes to form cavernous spaces in the glial scars following CNS injury and in the compressed optic nerve in glaucomatous optic nerve neuropathy.

Adult↗
PubMed2000

Control of extracellular matrix assembly by syndecan-2 proteoglycan.

Extracellular matrix (ECM) deposition and organization is maintained by transmembrane signaling and integrins play major roles. We now show that a second transmembrane component, syndecan-2 heparan sulfate proteoglycan, is pivotal in matrix assembly. Chinese Hamster Ovary (CHO) cells were stably transfected with full length (S2) or truncated syndecan-2 lacking the C-terminal 14 amino acids of the cytoplasmic domain (S2deltaS). No differences in the amount of matrix assembly were noted with S2 cells, but those expressing S2deltaS could not assemble laminin or fibronectin into a fibrillar matrix. The loss of matrix formation was not caused by a failure to synthesize or externalize ECM components as determined by metabolic labeling or due to differences in surface expression of alpha5 or beta1 integrin. The matrix assembly defect was at the cell surface, since S2deltaS cells also lost the ability to rearrange laminin or fibronectin substrates into fibrils and to bind exogenous fibronectin. Transfection of activated alphaIIbalphaLdeltabeta3 integrin into alpha(5)-deficient CHO B2 cells resulted in reestablishment of the previously lost fibronectin matrix. However, cotransfection of this cell line with S2deltaS could override the presence of activated integrins. These results suggest a regulatory role for syndecan-2 in matrix assembly, along with previously suggested roles for activated integrins.

Amino Acid Sequence↗
PubMed2002

Identification of genes responsive to sodium butyrate in colonic epithelial cells.

We identified genes responsive to sodium butyrate (SB) in colonic epithelial cells using cDNA microarrays. Treatment with 2 mM SB of colonic epithelial cells (MCE301), which was derived from transgenic mice harboring a temperature-sensitive simian virus 40 large T-antigen, arrested cell growth and showed a differentiated phenotype accompanying an increase in alkaline phosphatase activity. Of the approximately 900 genes analyzed, SB down-regulated 25 genes and up-regulated 88 genes by a factor of 2.0 or greater. Northern blot or TaqMan and Western blot analyses confirmed that the mRNA and protein levels of cyclin D1 and the level of proliferating cell nuclear antigen decreased, whereas the levels of integrin beta1 and osteopontin increased. The present results regarding the changes in gene expression, arrived at using microarrays, will provide a basis for a further understanding of the molecular mechanisms of cell growth arrest and differentiation in response to SB in colonic epithelial cells.

Alkaline Phosphatase↗
PubMed2001

Integrin- and cadherin-mediated induction of the matrix metalloprotease matrilysin in cocultures of malignant oral squamous cell carcinoma cells and dermal fibroblasts.

Matrilysin is a matrix metalloprotease (MMP) overexpressed in a number of cancers including skin, head and neck squamous cell carcinomas, and prostate and colon adenocarcinomas. Matrilysin has been shown to play a role in the degradation of the basement membrane that separates epithelium from stroma allowing tumor cells to intravasate into the bloodstream and metastasize. Here, we show that an oral squamous cell carcinoma cell line (SCC-25) expresses low levels of promatrilysin when cultured alone. However, when SCC-25 cells are cocultured with human foreskin fibroblasts (HFF), there is a 40-fold induction of promatrilysin expression. We tested whether this induction of promatrilysin expression was due to the release of paracrine factors, cell-cell interactions, or cell-matrix interactions. Our results indicate induced promatrilysin expression is the result of both cell-cell and cell-matrix interactions. We demonstrate that beta1 integrins as well as cadherins, specifically N-cadherin and E-cadherin, are involved in the induction of promatrilysin expression. Our results are of general interest in relation to the regulation of MMP expression through cell surface receptor regulation. Further investigation may lead to the identification of novel targets for suppression of invasion and metastasis in oral tumors.

Blotting, Western↗