Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin beta1”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,747 records · Page 97Linked to original sources
PubMed1993

Integrin expression in early amphibian embryos: cDNA cloning and characterization of Xenopus beta 1, beta 2, beta 3, and beta 6 subunits.

During embryogenesis cells modulate their adhesion to other cells and the surrounding extracellular matrix, in part, through the combination of integrins they express. In order to identify integrins that may mediate morphogenetic cell movements in the early Xenopus embryo, we have used polymerase chain reaction methods to isolate cDNAs encoding Xenopus integrin beta subunits. Based on deduced amino acid sequence, they are identified as homologs of human integrins beta 1, beta 2, beta 3 and beta 6. We also report the cloning and sequencing of cDNAs covering the complete coding region of Xenopus beta 3. Embryonic patterns of expression for these integrin beta subunit mRNAs have been examined both by RNase protection analysis and by whole mount in situ hybridization. In the early embryo the beta 1 subunit is encoded by a maternally transcribed mRNA expressed in all cells, but is most abundant in ectoderm and mesoderm. In contrast, Xenopus beta 3 mRNA is detected in the epidermis, bottle cells of the neural groove, and a subset of cells arising from the ventral blood islands. The beta 2 and beta 6 mRNAs are expressed at high levels in late tailbud stages, although very low levels of beta 6 are also detected in eggs and early embryos. These data provide evidence that multiple integrins are expressed at the earliest stages of vertebrate development coincident with the onset of morphogenesis.

Amino Acid Sequence↗
PubMed1994

Immunolocalization of basement membrane components and beta 1 integrin in the chick wing bud identifies specialized properties of the apical ectodermal ridge.

To examine whether the extracellular matrix (ECM) plays a role in mediating interactions between the apical ectodermal ridge (AER) and the subjacent mesoderm in the chick wing bud, we used immunohistochemistry to locate the following tissue components during wing morphogenesis: types I and IV collagens, fibronectin, the basal lamina form of heparan sulphate proteoglycan (HSPG), laminin, and the beta 1 integrin subunit. The notch region at the base of the AER exhibits particularly strong labelling for type IV collagen, fibronectin, laminin, and beta 1 integrin. This suggests that the ridge cells are firmly anchored to their underlying basement membrane. In nonridge ectoderm, the beta 1 integrin subunit is present only at the basal cell surface, whereas in the AER it has a pericellular distribution. The localization of beta 1 integrin receptors at the lateral ridge cell surfaces, in the apparent absence of fibronectin, collagens I and IV, and laminin, suggests that they may function in cell-cell adhesion in the AER. The normal AER-mesenchyme interface was compared to an experimental situation in which the AER flattens. This was induced in the anterior region of the wing bud by inserting an impermeable barrier at intersomite level 17/18, at stage 21. At 12 hr (stage 23) and 24 hr (stage 25) after the operation, each of the ECM components listed above is uniformly distributed along the experimental epithelial-mesenchymal interface. By 24 hr postoperation, the beta 1 integrin subunit is restricted to the basal surface of the flattened apical ectoderm. Similar changes occur in the AER as it flattens during later stages of normal development. These results point to a possible role for the ECM and integrin receptors in maintaining the thickened structure of the AER.

Animals↗
PubMed1993

Localization of beta 1-integrins in human cartilage and their role in chondrocyte adhesion to collagen and fibronectin.

In the past, proteins have been described that may be involved in chondrocyte interactions with extracellular collagen, but little is known about the role of integrins in chondrocyte-collagen interactions. Here we report on the analysis of beta 1-integrin distribution in human fetal cartilage and on the expression of integrins on fetal chondrocytes, using monoclonal and polyclonal antibodies to integrin alpha- and beta-chains. We show the presence of alpha 2-, alpha 5-, alpha 6-, alpha v-, and beta 1-chains on freshly isolated chondrocytes by surface immunofluorescence in the fluorescence-activated cell sorter and by surface iodination followed by immunoprecipitation. Affinity chromatography of bovine chondrocyte membrane proteins on a collagen-Sepharose column followed by immunoprecipitation confirmed the presence of the collagen-binding alpha 2 beta 1-integrin on chondrocytes. Chondrocyte adhesion on native collagens I and II, on fibronectin, and on laminin was completely blocked by anti-beta 1; anti-alpha 2 reduced chondrocyte binding to collagen by only 40-50%; similarly, anti-alpha 1-antibodies were also able to reduce chondrocyte binding to collagen, although alpha 1 could not be unequivocally identified on chondrocytes. Chondrocyte adhesion to fibronectin was Mg(2+)- and Ca(2+)-dependent and could be inhibited by anti-alpha 5 and by RGD peptides. Chondrocyte adhesion to native collagens is Mg(2+)-, but not Ca(2+)-dependent and RGD-independent. Interestingly, although these data point to a role of alpha 2 beta 1 in chondrocyte-collagen interactions in vitro, alpha 2 could not be visualized in sections of human fetal cartilage, in contrast to the beta 1-, alpha v-, and alpha 5-chains which were present. This suggests that alpha 2 beta 1-integrin may be involved in the assembly of a pericellular collagen matrix in vitro, but may not be required for chondrocyte-collagen interactions in intact cartilage.

Animals↗
PubMed1994

Cell-collagen adhesion is inhibited by monoclonal antibody 33.4 against the rat alpha 1-integrin subunit.

A monoclonal antibody (mAb 33.4) is described which inhibits the adhesion and spreading of an adherent cell line (A-cells), established from Morris hepatoma 7777 and isolated hepatocytes on collagen IV but not on laminin, fibronectin, and vitronectin. mAb 33.4 retains its immunological activity after immobilization and covalent cross-linking to Protein G-Sepharose and is therefore a suitable tool for the preparative equimolar purification of two proteins with M(r) of 130 and 190 kDa from detergent-solubilized membrane fractions by immunoaffinity chromatography. The 190-kDa protein was identified as rat alpha 1-integrin subunit by N-terminal amino acid sequencing, while the 130-kDa protein was specifically stained by a beta 1-integrin subunit-specific antiserum. In immunoblot analysis mAb 33.4 recognized the 190-kDa band, suggesting that it is specific for the rat alpha 1-integrin subunit. The epitope recognized by mAb 33.4 is conformation-dependent because the staining in immunoblots was very strong if the SDS-PAGE was performed in the absence of reducing agents. The expression of alpha 1 beta 1-integrin in sinusoidal hepatocyte membrane domains of liver sections is shown by mAb 33.4 and antisera raised against the rat alpha 1- and beta 1-integrin subunits.

Animals↗
PubMed1994

Activation of 72-kDa type IV collagenase/gelatinase by normal fibroblasts in collagen lattices is mediated by integrin receptors but is not related to lattice contraction.

The matrix metalloproteinase 72-kDa type IV collagenase (also known as gelatinase A) is thought to be involved in both normal connective tissue remodeling and invasive pathological processes. Like other matrix metalloproteinases, 72-kDa type IV collagenase is secreted by fibroblast monolayers as an inactive proenzyme, but is unique among this enzyme family in that it is not activated by serine proteinases such as plasmin. However, when fibroblasts are cultured in a collagen lattice, a situation thought to better approximate in vivo conditions, we have invariably found much of the secreted 72-kDa type IV collagenase in its enzymatically active 62-kDa form. Although collagen lattice contraction appeared to be required for the activation of 72-kDa type IV collagenase, we have found that the process of contraction can be dissociated from proenzyme activation. Both cytochalasin D and alpha-methylmannoside completely blocked lattice contraction, but not proenzyme activation. Furthermore, the monoclonal antibody M-13, which is directed against the beta 1 integrin chain, blocked collagen lattice contraction but not 72-kDa type IV procollagenase activation. At concentrations significantly higher than required to block lattice contraction or cell adhesion to collagen, M-13 was able to inhibit proenzyme activation. A second monoclonal antibody to the beta 1 integrin, P5D2, had little effect on collagen lattice contraction at low concentrations, but could significantly inhibit the activation of 72-kDa type IV procollagenase. Antibodies to the integrin alpha 2 chain also inhibited proenzyme activation. These data show that the activation of 72-kDa type IV collagenase proenzyme, like collagen lattice contraction, is mediated by beta 1 integrin receptors, possibly alpha 2 beta 1. Although both anti-beta 1 antibodies used are directed to the same site on the integrin chain, the fact that each antibody preferentially blocks a different event, either lattice contraction or activation of 72-kDa type IV collagenase, suggests the existence of branch points in the receptor-mediated signal transduction pathway.

Antibodies, Monoclonal↗
PubMed1994

Cell adhesion receptors for native and denatured type I collagens and fibronectin in rabbit arterial smooth muscle cells in culture.

Cell adhesion molecules serve as specific cell surface receptors for extracellular matrices and contribute to the attachment, spreading, proliferation, and differentiation of vascular cells. We examined the cell adhesion receptors and binding sites on native type I collagen, heat-denatured type I collagen, and fibronectin in rabbit arterial smooth muscle cells (SMC) in culture. On fibronectin, anti-alpha 3 beta 1 and anti-alpha 5 beta 1 integrin antibodies and the synthetic peptide GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro) significantly inhibited the attachment and spreading of rabbit SMC after 1 and 24 h of culture, while anti-alpha 1 beta 1 inhibited attachment and spreading only after 1 h. In contrast, the attachment and spreading of the cells on native type I collagen were mediated by alpha 1 beta 1 integrin and the cell-binding sequence which did not contain RGD (Arg-Gly-Asp) and DGEA (Asp-Gly-Glu-Ala) after both 1 and 24 h. On heat-denatured type I collagen, alpha 2 beta 1 integrin mediated the cell attachment and spreading after 1 and 24 h and DGEA served as a recognition site for the alpha 2 beta 1 integrin. alpha 1 beta 1 and alpha 3 beta 1 integrins affected only the initial adherence (1 h after plating) of the cells to denatured type I collagen. These findings suggest that rabbit SMC in culture can recognize the native and unfolded triple helical structures of type I collagen by interacting with the collagen fibril-binding receptor (alpha 1 beta 1 integrin) and collagen peptide-binding receptors (alpha 2 beta 1 and alpha 3 beta 1 integrins). Moreover, alpha 1 beta 1 integrin may mediate the initial adherence to each substrate.

Amino Acid Sequence↗
PubMed1994

Mg2+ and Ca2+ differentially regulate beta 1 integrin-mediated adhesion of dermal fibroblasts and keratinocytes to various extracellular matrix proteins.

The specific requirements for divalent cations in the integrin-dependent adhesion and deadhesion of human dermal fibroblasts and human epidermal keratinocytes to various extracellular matrix proteins have been studied in vitro. The adhesion of both cell types to collagen type I and to laminin was enhanced by Mg2+ in a concentration-dependent manner, while Ca2+ dose-dependently antagonized this effect, thus promoting deadhesion. The cation-dependent conversion between adhesion and deadhesion occurred already at 2 to 10 min after addition of the alternate cation and was almost completed at 20 min. Interestingly, Ca2+ could not reverse the Mg(2+)-enhanced adhesion of both cell types to fibronectin. Inhibition studies with function-blocking antibodies directed against distinct beta 1 integrins showed that the Mg(2+)-enhanced fibroblast adhesion to collagen type I was mediated by the alpha 1 beta 1 and the alpha 2 beta 1 integrins, whereas keratinocyte adhesion to collagen type I was mediated by the alpha 2 beta 1 integrin. Both cell types utilized the alpha 2 beta 1 and the alpha 6 beta 1 integrins for Mg(2+)-dependent adhesion to laminin and the alpha 5 beta 1 integrin for the adhesion to fibronectin. Integrin expression at the cell surface was not altered, indicating that divalent cation-dependent conformational changes of beta 1 integrins most likely regulate their functional activity.

Calcium↗
PubMed1994

Expression of N-CAM by human renal cell carcinomas correlates with growth rate and adhesive properties.

In the present study we provide evidence for the involvement of N-CAM in the spreading of human renal cell carcinomas (RCC) through the interaction with the subendothelial matrix. We found that in tumor cell lines derived from human RCC the increase of growth rate and the loss of adhesiveness to inert substrate were accompanied by N-CAM expression and by the appearance of specific binding to endothelial heparan sulfate. Indeed, the adhesion of tumor cells to human endothelial cells and heparan sulfate in vitro was inhibited by monoclonal antibodies able to bind and inactivate N-CAM and was abrogated by endothelial cell treatment with heparitinase. Furthermore, when the renal epithelial cell line COS7 was transfected with a cDNA coding for N-CAM a significant increase in the ability to bind both endothelium and heparan sulfate in vitro was observed. Of note, HS complexed with epithelial growth factor could enhance the proliferation of RCC-derived tumor cells; this effect was also achieved by cross-linking of N-CAM at the surface of tumor cells, suggesting that N-CAM could transduce an activation signal across the cell membrane. This was also supported by the finding that N-CAM cross-linking induced a strong calcium mobilization from internal stores and opening of surface calcium channels in such tumor cells. N-CAM was detectable in vivo at the tumor site in the areas of active proliferation, as judged by the coexpression of Ki67 nuclear antigen, and heparan sulfate was present in the wall of blood vessels in the proximity of the tumor. These findings would suggest that growing kidney tumors might use N-CAM to bind the subendothelial matrix and complexed growth factors during tissue invasion and spreading.

Carcinoma, Renal Cell↗
PubMed1994

Platelet-derived growth factor-BB stimulates synthesis of the integrin alpha 2-subunit in human diploid fibroblasts.

Platelet-derived growth factor (PDGF)-BB stimulates fibroblast-mediated contraction of collagen gels, as well as migration of fibroblasts through collagen-coated membranes. In the present study we examined effects of PDGF-BB stimulation on the synthesis of collagen-binding beta 1 integrins by human diploid fibroblasts (AG 1518). PDGF-BB stimulation led to an increase in the rare of integrin alpha 2-subunit synthesis. In contrast, synthesis of the integrin alpha 1- or alpha 3-subunits were not affected by PDGF-BB stimulation. Furthermore, levels of alpha 2-subunit mRNA relative to levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA increased after PDGF-BB stimulation. The latter finding is compatible with PDGF-BB stimulating transcription of the alpha 2-subunit gene. PDGF-BB stimulation did not influence the relation between levels of integrin beta 1-subunit mRNA and GAPDH mRNA. In addition, the rate of synthesis or post-translational processing of the integrin beta 1-subunit were not, or only marginally, affected by PDGF-BB stimulation. It is likely that the motility response elicited in fibroblasts by PDGF-BB involves such alterations in the synthesis of the alpha 2-subunit of the alpha 2 beta 1 collagen-binding integrin.

Becaplermin↗
PubMed1995

Epidermal growth factor enhancement of HSC-1 human cutaneous squamous carcinoma cell adhesion and migration on type I collagen involves selective up-regulation of alpha 2 beta 1 integrin expression.

Some human neoplasms show aberrant expression or overexpression of epidermal growth factor (EGF) receptor, and the degree of the receptor expression is correlated with the malignant phenotype in certain epithelial tumors including squamous carcinoma cells. Since phenotypic transformation of cells could involve quantitative and qualitative alteration of integrin function, the effects of EGF on cell-matrix interactions were studied using HSC-1 cells, a human squamous carcinoma cell line showing EGF receptor overexpression. The EGF-treated HSC-1 cells interacted with matrix proteins differently from the untreated cells, as shown by cell adhesion and phagokinetic track assays. Among fibronectin, laminin, fibrinogen, and type I collagen, fibronectin was the most efficient substratum to promote untreated HSC-1 cell adhesion and migration. Pretreatment of the cells with 50 ng/ml EGF for 18 h selectively increased the number of spread cells and the size of the individual cell migration area on type I collagen by 250 and 400%, respectively. The same pretreatment diminished cell adhesion and migration on other substrata so that the EGF treatment converted type I collagen as the most efficient substratum for cell adhesion and migration of the HSC-1 cells. ELISA and immunoprecipitation studies showed that EGF up-regulated the expression of alpha 2 beta 1 integrin collagen receptor in a time- and dose-dependent manner by stimulating biosynthesis of alpha 2 subunit, but did not up-regulate those of the alpha 3 beta 1, alpha 5 beta 1, or alpha v beta 3 integrins. These results suggest that EGF preferentially enhances HSC-1 cell interaction with type I collagen, leading to the enhanced cellular migratory activity on the substratum, as a result of selective up-regulation of alpha 2 beta 1 integrin expression.

Antigens, CD↗
PubMed1995

Expression of beta 1 integrins by cultured articular chondrocytes and in osteoarthritic cartilage.

Expression of beta 1 integrins was studied in vitro as articular chondrocytes reestablished a matrix in culture and in situ in a nonhuman primate model of osteoarthritis in order to investigate a potential role for integrins in mediating cell-extracellular matrix interactions in cartilage. Chondrocytes were found to express alpha 1 beta 1, alpha 3 beta 1, and alpha 5 beta 1 integrins both in vitro and in situ. Cell surface expression of beta 1 integrins increased as chondrocytes were maintained in cultured from 3 to 7 days. Increased beta 1 integrin expression was also observed in osteoarthritic cartilage compared with normal cartilage. The greatest relative increase in both systems was noted for the alpha 1 beta 1 integrin. The increase in chondrocyte beta 1 integrin expression in vitro was noted in both monolayer and alginate cultures and occurred prior to detectable changes in the differentiated phenotype of the chondrocyte. Disruption of the cytoskeleton with the drug dihydrocytochalasin B inhibited the cell culture induced increase in integrin expression, while treatment of cultured cells with TGF-beta resulted in increased expression of the alpha 5 beta 1 integrin. The modulation of beta 1 integrin expression noted in vitro and in situ indicates that chondrocytes are capable of regulated expression of beta 1 integrins and suggests that beta 1 integrins may play an important role in mediating chondrocyte-extracellular matrix interactions in cartilage.

Animals↗
PubMed1995

Expression and function of beta 1 integrins on adherent and nonadherent Ehrlich ascites tumor cells.

Differences in integrin-mediated cell-matrix adhesion between two types of Ehrlich ascites tumor (EAT) cells, adherent and nonadherent EAT cells, have been studied. The adherent EAT (a-EAT) cells adhere to and spread on laminin- or fibronectin-coated plates, whereas the nonadherent EAT (na-EAT) cells do not. The adhesion of a-EAT cells to laminin or fibronectin requires the presence of both Ca2+ and Mg2+. Anti-human fibronectin receptor (alpha 5 beta 1 integrin) antiserum blocks a-EAT cells from adhering to both laminin- and fibronectin-coated plates. An RGD-containing peptide (GRGDSP) inhibits the adhesion of a-EAT cells to fibronectin-coated but not to laminin-coated plates. Taken together, these data suggest that a-EAT cells interact with laminin and fibronectin via different beta 1 integrins. As determined by immunofluorescence flow cytometry assay, both a-EAT and na-EAT cells express similar amounts of surface antigen(s) recognized by the same anti-alpha 5 beta 1 integrin polyclonal antibody that blocks a-EAT cells from adhering to laminin and fibronectin. The alpha 5 and beta 1 subunits expressed on both types of EAT cells appear to have the same molecular weight when analyzed by immunoblotting. The same amount of 125I-labeled membrane protein was isolated from both types of EAT cells on immobilized laminin and fibronectin affinity columns. These data indicate that na-EAT cells express similar amounts of cell surface integrins, and these integrins, when isolated, react with laminin and fibronectin in the same manner as the integrins of a-EAT cells, even though na-EAT cells are unable to adhere to laminin and fibronectin. Previous work has shown that both types of EAT cells express Neu5Ac alpha 2,3 Gal-beta 1, 4 GlcNAc residues on their cell surface and that they both react with Maackia amurensis lectin which specifically recognizes this carbohydrate structure. Here we show that both types of EAT cells attach to M. amurensis lectin-coated surfaces, but only a-EAT cells spread; this suggests that the differences between these two types of cells in responding to extra cellular matrix molecules may reside in some differences within the cell.

Animals↗
PubMed1995

Mechanical induction of beta 1-integrin-mediated calcium signaling in a hepatocyte cell line.

Mechanical stress influences growth, differentiation, and gene expression in a variety of cell types. It is believed that via extracellular matrix the mechanical stimulus is transmitted to integrin receptors which thus play a key role in transducing signals into the cell interior. Here we demonstrate that incubation of suspended hepatocytes with specific antibodies to beta 1-integrin subunits followed by a short-term mechanical stimulation is sufficient to induce a rise in intracellular Ca2+. The results indicate that mechanical loading of individual integrin subunits activates Ca(2+)-specific signal pathways.

Animals↗
PubMed1995

Beta 1 integrins in epithelial tissues: a unique distribution in the lens.

Integrins have been shown to play a role in directing and maintaining cell differentiation and polarization. The embryonic lens provides a good system in which to examine their role in epithelial cell differentiation, because all stages of lens development are represented in an individual embryonic lens. Therefore, we examined the expression and distribution of beta 1 integrin heterodimers in both the lens epithelium and the differentiated lens fiber cells. In lens epithelial cells beta 1 integrin was found to be localized to all membrane surfaces. Lens fiber cells contained beta 1 integrin all along their lateral borders as well as at the site of their attachment to the lens capsule and at their interface with lens epithelial cells. The distribution of beta 1 integrin in the lens was distinct from that observed in simple epithelia, the retinal pigment epithelium (RPE), kidney, and intestine, where it was limited to a basal lateral localization. We examined the specific beta 1 integrin heterodimers expressed in the lens by Western blot analysis for the integrin alpha subunits following beta 1 immunoprecipitation and compared them with those expressed in RPE cells. In the lens we detected alpha 3 and alpha 6 subunits but not alpha 1, alpha 5, or alpha v. When the lens was separated into epithelial and fiber cells, we found that alpha 3 was expressed at a higher level in the epithelial cells, while alpha 6 was primarily associated with the fiber cells. In the RPE the primary beta 1 integrin detected was alpha 3. Unlike in lens and kidney, alpha 6 beta 1 integrin in RPE cells was expressed only at a low level. alpha v was also expressed in RPE cells but not as a beta 1 heterodimer. As in the lens, neither alpha 5 beta 1 nor alpha 1 beta 1 integrin was detected in RPE. Both lens and RPE cells express a specific subset of beta 1 integrin heterodimers which are likely to be important to the initiation and maintenance of their differentiated phenotype.

Animals↗
PubMed1995

pp125FAK in human melanocytes and melanoma: expression and phosphorylation.

Focal adhesion kinase (pp125FAK) is a nonreceptor tyrosine kinase which colocalizes with integrins to focal contacts, sites where multiple proteins interact to regulate the assembly of the actin cytoskeleton. Autophosphorylation and activation of pp125FAK occur after integrin clustering or cell adhesion to ligands through cognate integrin receptors and are postulated to mediate integrin signaling events. In this report we examined pp125FAK expression and phosphorylation in normal human melanocytes, an adherent human metastatic melanoma cell line (SKMEL28), and a nonadherent human metastatic melanoma cell line (SKMEL1). We show that SKMEL28 cells express constitutively phosphorylated pp125FAK and that pp125FAK phosphorylation in melanocytes is induced by phorbol esters and growth factors present in melanocyte growth medium. Focal adhesion kinase phosphorylation could be enhanced by b1 integrin-activating antibodies in human melanocytes, but not in SKMEL28 cells. In contrast with SKMEL28 cells, constitutive phosphorylation of pp125FAK was not observed in SKMEL1 cells, and incubation with activating b1 integrin antibodies had no effect on pp125FAK phosphorylation. Absence of pp125FAK phosphorylation in SKMEL1 cells was not due to lack of expression of pp125FAK, as shown by immunoprecipitation of the pp125FAK protein from cell lysates. However, b1 integrin expression was significantly less in SKMEL1 cells than in human melanocytes and SKMEL28 cells. This study further supports the importance of integrins in pp125FAK-mediated signaling and indicates that transformation-related changes in pp125FAK phosphorylation exist in human melanocytes and melanoma cells.

Antibodies↗
PubMed1995

Beta 1 integrins do not have a major role in keratinocyte intercellular adhesion.

Integrins of the epidermis have been implicated both in intercellular adhesion and in cell-substratum adhesion. In the present study the role of alpha 2 beta 1 and alpha 3 beta 1 integrins has been evaluated further using human keratinocyte culture. alpha 3 beta 1 but not alpha 2 beta 1 strongly colocalizes with talin in adhesion plaques, consistent with a role for the former in adhesion to endogenous matrix. Upon elevation of the extracellular Ca2+ concentration from 30 microM to 1.0 mM, which is known to induce the organization of intercellular junctions, all three integrin subunits redistribute to concentrate along the cell-cell borders, but alpha 3 redistributes more slowly. Blocking antibody to E-cadherin, which has previously been shown to delay the establishment of cell-cell adhesion upon Ca2+ elevation, delays the redistribution of alpha 2 beta 1 and alpha 3 beta 1 integrins. Elevation of the Ca2+ concentration also induces a rapid morphological change in the keratinocytes and organization of the culture into colonies with tight cell-cell connections. Blocking antibodies to beta 1 or to alpha 3, but not to alpha 2, delays this morphological change and the organization into colonies; however, the effect is much more pronounced in subconfluent cultures. These data are consistent with the hypothesis that anti-beta 1 or anti-alpha 3 antibodies affect cell-cell interactions primarily through their previously described inhibition of motility. Stratification of the culture, which follows the formation of intercellular interactions, is normal in the presence of blocking antibody to beta 1 integrin. In summary, these data suggest that integrins do not play a major role in intercellular keratinocyte adhesion, but may appear to do so under certain conditions because of their involvement in motility.

Antibodies↗
PubMed1995

Induction of beta 1 integrin synthesis by recombinant platelet-derived growth factor (PDGF-AB) correlates with an enhanced migratory response of human dermal fibroblasts to various extracellular matrix proteins.

Cell migration plays a major role during wound healing and is tightly controlled by a variety of growth factors and extracellular matrix proteins. The experiments reported here have been designed to study whether defined beta 1 integrins are involved in the platelet-derived growth-factor-AB (PDGF-AB)-modulated migratory response to collagen type I and to fibronectin. Preincubation of fibroblasts with PDGF-AB resulted in an up to 2.5-fold increase in the migratory response to collagen type I as well as fibronectin and to enhanced synthesis and cell surface expression of the alpha 2, alpha 3, alpha 5, and beta 1 integrin subunits. Function-blocking monoclonal antibodies against the common beta 1 integrin subunit dose-dependently inhibited the PDGF-AB-augmented migration of fibroblasts to collagen type I and fibronectin. The PDGF-AB-induced migration to collagen type I was also inhibited by antibodies against the alpha 2 integrin subunit, whereas the corresponding migration to fibronectin was almost completely blocked by the combined application of antibodies against the alpha 3 and the alpha 5 integrin subunits. Taken together, up-regulation of integrin synthesis and expression by human recombinant PDGF-AB correlate with an increase in the migratory response of dermal human fibroblasts to various extracellular matrix proteins and thus may contribute to an efficient regulation of cell migration during wound healing and tissue repair.

Cell Movement↗
PubMed1995

Cell-to-cell contact modulates the expression of the beta 1 family of integrins in primary cultures of thyroid cells.

The expression of the beta 1 family of integrins was studied in normal thyroid tissue cultures and monolayer cell cultures. The expression of the various subunits was measured by flow cytofluorometry with specific monoclonal antibodies and by Northern analysis. In monolayer cell cultures but not in tissue cultures, the expression of the alpha 3 subunit on the cell membrane progressively increased soon after plating, reaching a 30-fold higher intensity. The alpha 2 subunit, not detectable in native follicular cells, was expressed de novo and reached a remarkable high level. Up-regulation of alpha 2 and alpha 3 in monolayer cell cultures was serum-independent and preceded the expression of proliferating cell nuclear antigen, [3H]thymidine incorporation, and cell replication. Northern analysis demonstrated an increased level of beta 1 integrin mRNA. The increase of alpha 2 and alpha 3 was readily reversible since the expression of these molecules returned to a lower level when cultures reached a high cell density. Down-regulation did not occur until cell cultures were confluent. When cells from high cell density and low integrin expression were harvested and sparsely seeded in culture, up-regulation of integrins was observed again, while rapid reaggregation of isolated cells inhibited this phenomenon. Altogether these data suggest that cell-to-cell contact may regulate the expression of beta 1 integrins in thyroid primary cultures.

Antigens, CD↗