Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin alpha3beta1”

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 361 records · Page 20Linked to original sources
PubMedDate not supplied

Localization of the alpha 3 beta 1 integrin in some common epithelial tumors of the ovary and in normal equivalents.

Monoclonal antibodies (mAbs) against cultured human ovary carcinoma cells were produced. We obtained 7 mAbs which reacted diffusely with carcinoma of the ovary but only weakly with vessels and the surface epithelial layer of normal ovary. Biochemical characterization of these mAbs indicated that 3 out of 7 were specific for the alpha 3 chain of the Vla-3 integrin, a receptor for fibronectin, collagen and laminin. Using one of these mAbs, we have studied, by immunohistochemical methods, the distribution of alpha 3 beta 1 integrin in mucinous, serous and endometrioid cystoadenocarcinoma of the ovary and in their normal equivalent: endocervical, tubal and endometrial epithelia. The results show that alpha 3 beta 1 is present in cell-cell contact areas and more abundantly at the junction between epithelial cells and basement membrane in endocervical, tubal epithelia, in epithelium lining the cavity of the uterus and in surface epithelium of the ovary. However, endometrial glands showed only weak and fragmented positivity at the basal pole of the cells. 26 out of 31 ovarian cancers studied, expressed the alpha 3 beta 1 integrin. However, basal localization, typical of normal epithelia, is not prominent or disappears in tumors and is replaced by a more diffuse reaction with variable immunohistochemical staining of the neoplastic cells. Furthermore, a comparative analysis of the expression of alpha 3 beta 1 and its ligands, laminin (LM), fibronectin (FN) and collagen IV (Coll IV), demonstrated that basal polarization of Vla-3 was always correlated with the presence of laminin and Coll IV, intrinsic components of the basement membranes.

Amino Acid Sequence↗
PubMed1995

Alteration of epidermal differentiation in middle ear cholesteatoma.

This immunohistologic study was undertaken to compare the localization of markers of epidermal differentiation in cholesteatoma and normal external ear canal skin. Both basal cells and suprabasal cell layers of cholesteatoma exhibit an abnormal distribution of differentiation markers (involucrin, filaggrin, glycoproteins detected by monoclonal antibodies J143 [alpha3 integrin chain] and T16 [Trop-2]). The immunostaining intensity of filaggrin and involucrin was higher in cholesteatoma than in external ear canal skin. In cholesteatoma, involucrin was localized in the cytoplasm of the suprabasal cells, and particularly in spinous cells, it appeared earlier than in ear canal skin. Filaggrin was noted in the cytoplasm of the granular and cornified cells in both tissues. The J143 reactive integrin, very late antigen 3 (VLA-3), which in normal epidermis is confined to the basal cells, was also seen in spinous and granular cell layers of cholesteatoma. Furthermore, the immunostaining for VLA-3 in the basal cell layer of cholesteatoma was stronger than in normal epidermis. In contrast to this, expression of Trop-2, which is preferentially found in the suprabasal cell layers, particularly in granular cells of normal epidermis, was clearly reduced in cholesteatoma. These results demonstrate complex alterations in the differentiation of the keratinocytes in cholesteatoma.

Antigens, Neoplasm↗
PubMed1996

Selective changes in laminin adhesion and alpha 6 beta 4 integrin regulation are associated with the initial steps in keratinocyte maturation.

In skin, the distribution of integrins is compartmentalized. Whereas the alpha 6 beta 4 integrin complex is polarized to the basal portion of proliferating cells in the basal layer juxtaposed to the basement membrane, alpha 3 beta 1 integrin receptors are localized on the cell surface surrounding basal and suprabasal cells, suggesting beta 1 integrins mediate both cell-matrix and cell-cell interactions. As initiation of maturation in skin is associated with the detachment of cells from the basement membrane, the early loss of alpha 6 beta 4, but not alpha 3 beta 1, integrin expression could be a determining factor in the transition from the proliferating to a differentiating keratinocyte. We have studied the regulation of adhesion potential and integrin expression during differentiation of mouse basal keratinocytes culture in 0.05 mM Ca2+ medium and induced to differentiate in 0.12 mM Ca2+ medium. Within 12-24 h after elevation of Ca2+, a selective loss of the alpha 6 beta 4 integrin complex is associated with the induction of the spinous cell marker keratin 1. This early differentiation phenotype coincides with loss of cell attachment mediated by alpha 6 beta 4 to laminins 1 and 5 but not a fibronectin or collagen IV. Selective loss of attachment to laminin is also detected in spinous cells isolated from newborn epidermis in vivo. The loss of alpha 6 and beta 4 protein expression is a consequence of transcriptional and posttranscriptional events, including reduction in mRNA transcripts, reduced synthesis of the alpha 6 protein, and enhanced processing of the alpha 6 and beta 4 chains as determined by Western blots and pulse-chase experiments in metabolically labeled keratinocytes. Selective processing of the beta 4 intracellular domain is detected before loss of beta 4 from the cell surface in basal keratinocytes, and this process is accelerated during differentiation. Whereas early keratinocyte maturation is linked to the selective loss of the alpha 6 beta 4 complex, loss of both beta 1 and beta 4 integrin mRNA and protein occurs as cells proceed to later stages in the differentiation program as induced by 0.5 mM Ca2+ or suspension culture. These conditions are characterized by accelerated expression of transglutaminase; reduced keratin 1 protein; loss of adhesion to fibronectin, laminin 1, laminin 5, and collagen IV; and rapid cell death. Contributing to the down-regulation of beta 1 integrins during terminal differentiation is a selective sensitivity of alpha 3 beta 1 but not alpha 6 beta 4 to down-regulation by transforming growth factors beta 1 and beta 2, factors that are also expressed differentially in normal skin. This study indicates that down-regulation of the alpha 6 beta 4 but not beta 1 integrins occurs during the initial steps of keratinocyte differentiation and is associated with detachment from the laminin matrix. Such changes could contribute an important signal to initiate the process of terminal keratinocyte differentiation.

Animals↗
PubMedDate not supplied

Fibronectin modulates interleukin 6 and fibronectin synthesis of human glomerular mesangial cells in culture.

In this paper we report that fibronectin (FN) and its proteolytic 120-kD fragment regulate synthesis and secretion of interleukin 6 (IL-6) and of FN by human glomerular mesangial cells. While intact FN and a fragment derived from the heparin-binding domain had no effect on IL-6 secretion, the 120-kD FN fragment containing the cell attachment site stimulated secretion by 40-fold. The same FN fragment reduced FN secretion and the steady state mRNA level by 80%. The intact FN showed only a weak inhibitory effect (+/- 30%); the 30-kD fragment containing the heparin-binding domain had no effect. The effects of the 120-kD FN were inhibited by the peptide RGDS, implying participation of the cell attachment site in signal transduction. An antibody to the alpha-chain of VLA-3 mimicked the effect of the 120-kD FN, whereas an antibody to the alpha-chain of VLA-5 was partly inhibitory. Taken together, the data suggest that FN by interacting with its receptors differentially regulates the protein synthesis of glomerular mesangial cells, promoting IL-6 secretion and inhibiting FN synthesis.

Antibodies↗
PubMed1997

Intestinal epithelial restitution. Involvement of specific laminin isoforms and integrin laminin receptors in wound closure of a transformed model epithelium.

Disruptions in the mucosal lining of the gastrointestinal tract reseal by epithelial cell migration, a process termed restitution. We examined the involvement of laminin isoforms and their integrin receptors in restitution using the intestinal epithelial cell line T84. T84 cells express primarily laminins 5, 6, and 7 as indicated by immunostaining using laminin subunit-specific monoclonal antibodies (MAbs). A MAb (BM2) specific for the laminin alpha 3 subunit, a component of laminins 5, 6, and 7, completely inhibited the closure of mechanical wounds in T84 monolayers. Confocal microscopy using MAbs BM2 (laminin alpha 3 subunit) and 6F12 (laminin beta 3 subunit) revealed that laminin-5 is deposited in a basal matrix that extends into the wound. The MAbs 4E10 (laminin beta 1 subunit) and C4 (laminin beta 2 subunit) stained the lateral membranes between T84 cells. This staining was enhanced in cells adjoining wounds. Because T84 cells stained faintly with MAbs 4C7 (laminin alpha 1 subunit) and with MAbs 4F11 and 1B4 (laminin alpha 2 subunit), we suggest that expression of laminins 6 and 7 is enhanced in response to wounding. The alpha 3 beta 1 integrin and the alpha 6-containing integrins function in wound closure because MAbs specific for the beta 1 integrin subunit (MAb13), the alpha 3 subunit (IVA5), and the alpha 6 subunit (2B7) potently inhibited T84 migration into wounds. Immunofluorescence using UMA9, a beta 4-integrin-specific MAb, revealed that alpha 6 beta 4 integrin exists in a Triton-X-100-insoluble structure at the basal surface and that the staining of this structure is enhanced in cells adjoining wounds. In addition, a Triton-X-100-soluble pool of alpha 6 beta 4, as well as alpha 3 beta 1 and presumably alpha 6 beta 1, was found along lateral surfaces of T84 cells. On flattened cells adjoining wounds, staining for these integrins was distributed diffusely, suggesting a redistribution that accompanies cell migration. Taken together, these data suggest that wound-induced epithelial cell migration is a finely tuned process that is dependent upon the regulated function and localization of specific laminins and their integrin receptors.

Antigens, CD↗
PubMed1997

The A and B variants of the alpha 3 integrin subunit: tissue distribution and functional characterization.

The alpha subunits of the laminin-binding integrins alpha 3 beta 1, alpha 6 beta 1, and alpha 7 beta 1 have homologous sequences and are similar in structure. Two cytoplasmic variants, A and B, have been identified for each of these alpha subunits, although the alpha 3B splice variant has been detected only at the mRNA level. We prepared a panel of mouse monoclonal antibodies specific for the A and B variants of the alpha 3 subunit to study their tissue distribution. Four monoclonal antibodies react with alpha 3A, one of which recognizes only the nonphosphorylated form; of the three anti-alpha 3B antibodies, one cross-reacts with alpha 6B. Reverse transcriptase-PCR analysis of various human tissues revealed the presence of alpha 3B mRNA in brain, heart, and skeletal muscle. Moreover, the alpha 3B protein was detected by immunoblotting in brain and heart tissue but not in skeletal muscle. In contrast, alpha 3A mRNA and protein were present in all tissues studied. Thus, the expression of alpha 3B in adult tissues is more restricted than that of alpha 3A. Immunohistochemical studies showed that in brain tissue, both variants are exclusively expressed on small blood-vessel endothelium, whereas in heart tissue their distribution patterns differ markedly. Although alpha 3A is strongly expressed on vascular smooth muscle cells, alpha 3B is detected only on endothelial cells of veins. Expression of the two variant forms of alpha 3 in K562 cells revealed that the ligand-binding specificities of alpha 3A beta 1 and alpha 3B beta 1 are identical: both bind human laminin-2 and -4, laminin-5, and laminins isolated from bovine kidney, but not bovine laminin-2 and -4, mouse laminin-1, or human fibronectin. In addition, adhesion mediated by both integrins is induced to the same extent by phorbol 12-myristate 13-acetate. The alpha 3A, but not the alpha 3B subunit, is phosphorylated; and phosphorylation of alpha 3A increases after phorbol 12-myristate 13-acetate stimulation. Thus, we found no differences between the adhesion functions of the A and B variants of alpha 3.

Amino Acid Sequence↗
PubMed1997

Integrated expression of glomerular extracellular matrix proteins and beta 1 integrins in monoclonal light chain-related renal diseases.

Light-chain deposition disease (LCDD) and amyloid light-chain amyloidosis (AL-Am) represent the two classical diseases associated with glomerular alterations in monoclonal light chain-related renal diseases. LCDD is characterized by deposition of extracellular matrix proteins in the mesangium, thus creating the morphologic appearance recognized as nodular glomerulosclerosis. In AL-Am, the mesangial matrix is replaced by polymerized light chains in the form of amyloid fibrils. Integrins are responsible for cell-to-cell and cell-to-matrix communication and, therefore, are expected to play a key role in the alterations encountered in these two diseases. The present article addresses the expression of selected extracellular matrix proteins (collagen IV, laminin, fibronectin, and tenascin) and their respective receptor beta 1 integrins (alpha 2, alpha 3, alpha 5, and alpha 9) in glomeruli with LCDD and AL-Am by immunohistochemical methods. The corresponding integrin (alpha 9 beta 1) co-localized with tenascin in the center of the mesangial nodules in LCDD. In AL-Am, tenascin is found primarily at the periphery of replaced mesangial areas and in the remaining mesangium not replaced by the amyloid. Tenascin co-localized with alpha 9 beta 1 integrin in mesangial areas in the earlier phases of the process. Fibronectin, laminin, and collagen IV, although increased in absolute amounts, are pushed toward the periphery of mesangial areas, in which correlated expression of their corresponding beta 1 integrins (alpha 2, alpha 3, and alpha 5, respectively) is documented in both LCDD and AL-Am. Deposition of tenascin might be at least partially responsible for the perpetuation and irreversibility of the glomerular lesion in LCDD.

Albumins↗
PubMed1997

Expression of tetra-spans transmembrane family (CD9, CD37, CD53, CD63, CD81 and CD82) in normal and neoplastic human keratinocytes: an association of CD9 with alpha 3 beta 1 integrin.

Tetra-spans transmembrane family (TSTF) members (CD9, CD37, CD53, CD63, CD81 and CD82) have potent effects on cell growth, motility and adhesion in various cells. However, little is known about their expression in human skin. Using immunohistological techniques, we have studied the localization of all six members of TSTF in normal and carcinomatous human keratinocytes. CD9, CD81 and CD82 were expressed in the entire living layers of the epidermis. Their staining pattern was quite similar, and was mainly intercellular with occasional intracellular immunoreactivity. CD53 expression was confined to the intercellular spaces of the upper spinous or granular layer in the normal epidermis. No clear-cut expression of CD63 could be detected in the epidermis. CD37 was not detected at all. Cultured human keratinocytes also expressed CD9, CD81 and CD82 at the surface membrane of cell-cell boundaries. Expression of CD37 and CD53 was negative in cultured keratinocytes, while CD63 was clearly localized in the cytoplasmic lysosomes. An immunoprecipitation assay revealed that alpha 3 beta 1 integrin is molecularly associated with CD9. The expression of CD9, CD81 and CD82 was markedly down-regulated in basal cell carcinoma but not in Bowen's disease. The abundant and differential expression of TSTF molecules and the selective association of CD9 with alpha 3 beta 1 integrin suggest that the TSTF molecules may be involved in the regulation of epidermal differentiation and integrity in vivo.

Antigens, CD↗
PubMed1998

Identification and functional characterization of two type VI collagen receptors, alpha 3 beta 1 integrin and NG2, during avian corneal stromal development.

PURPOSE: The development and maintenance of extracellular matrix architecture in the corneal stroma is associated with abundant type VI collagen deposition. This collagen has been implicated in mediating both cell-matrix and matrix-matrix interactions. Although corneal fibroblasts spread extensively on this collagen, its role in corneal development has not been elucidated. METHODS: To clarify the role of this collagen, two type VI collagen receptors were studied during corneal development using immunochemical techniques: alpha 3 beta 1 integrin and an integral membrane proteoglycan, NG2. RESULTS: At embryonic day 6, these receptors were present in a diffuse pattern on cells within the cornea and juxtacorneal regions, indicating a migratory phenotype. At embryonic day 14, when the stroma is fully differentiated, alpha 3 and NG2 were localized in a punctate pattern on a subset of corneal fibroblasts, whereas beta 1 was more ubiquitously expressed. Colocalization of NG2 and type VI collagen indicated that this collagen was present and punctate in its organization was associated with NG2-positive cells. Immunochemical analyses at embryonic days 5 and 14 revealed alpha 3 and beta 1 at 155 kDa and 120 kDa, respectively, and demonstrated that these subunits were interacting to form a heterodimer. NG2 was present with a core protein of 330 kDa and an intact proteoglycan of approximately 600 kDa, and analysis of stromal lysates indicated a chondroitin sulfate-containing proteoglycan. Matrix-receptor cross-linking demonstrated the interaction of beta 1 and NG2 in periocular mesenchyme cells and corneal fibroblasts with type VI collagen, whereas only a subset of cells expressed alpha 3, indicating the presence of another beta 1 integrin. No variations between in vivo and in vitro expression of either alpha 3 beta 1 or NG2 were observed. CONCLUSIONS: These data indicate that two receptors for type VI collagen, alpha 3 beta 1 and NG2, are present during corneal stromal development, with a functional interaction of these receptors with type VI collagen. These interactions may play a role in corneal cell migration, development, and maintenance of corneal architecture.

Animals↗
PubMed1998

Thymocyte contact or monoclonal antibody-mediated clustering of 3beta1 or 6beta4 integrins activate interleukin-6 (IL-6) transcription factors (NF-kappaB and NF-IL6) and IL-6 production in human thymic epithelial cells.

T-cell precursors develop within the thymus in contact with multiple supportive elements, among which thymic epithelial cells (TEC) are known to exert a dominant role in their homing, survival, and functional differentiation. All these functions are supported by cell-cell contacts and cytokine release. Signaling events triggered in lymphoid cells by adhesion to TEC are well characterized, but little is known about the opposite phenomenon. To address this issue, we derived cultures of TEC from human normal thymus. TEC monolayers were cocultured with thymocytes and immunostained with monoclonal antibodies (MoAbs) to integrin (2, 3, 4, and 6) and beta (beta1 and beta4) chains. Optical and confocal analysis showed that integrins were polarized on TEC at discrete surface locations: 6beta4 lined the basal surface of TEC monolayers, whereas 3beta1 was found mostly at TEC-TEC contacts; it is noteworthy that both 3beta1 and 6beta4 became highly enriched also at the boundaries with adherent thymocytes. Functional studies performed with MoAbs anti-beta1 and -beta4 integrins showed that beta1, and, to a much lower extent, beta4 heterodimers are involved in the TEC-thymocyte adhesion. Thymocyte contact or MoAb-mediated ligation of 3, 6, beta1, and beta4 integrins was investigated as a potential inducer of intracellular signaling in TEC. Thymocyte adhesion or cross-linking of MoAbs bound to integrins clustered at the TEC/thymocyte contact sites led to activation of interleukin-6 (IL-6) gene transcription factors, namely NF-IL6 serine phosphorylation and NF-kappaB nuclear targeting, as well as to increased IL-6 secretion. We propose that integrin clustering occurring during TEC-thymocyte contacts modulates in TEC the gene expression of a cytokine involved in thymocyte growth and functional differentiation.

Antibodies, Monoclonal↗
PubMed1998

Neuronal receptors mediating responses to antibodyactivated laminin-1.

Embryonic retinal neurons lose the ability to extend neurites on laminin-1 (LN-1) with increasing developmental age yet still do so on other laminin isoforms. However, after treatment of LN-1 with antibodies to "short-arm" regions or removal of the short arms proteolytically, LN-1 supports attachment and extension of neurites even by late embryonic retinal neurons. We have mapped a domain for antibody-mediated "activation" of LN-1 to the N-terminal end of the alpha1 chain. Furthermore, we show that the primary receptors used in the retinal neuron response to "activated" LN-1 are integrins alpha3 beta1 and alpha6 beta1; these are the same receptors used by these neurons for outgrowth on other LN isoforms. Interestingly, alpha3 beta1 is preferentially involved in neurite outgrowth, whereas alpha6beta1 preferentially mediates attachment and spreading. However, in cultures from alpha3 integrin-deficient mice, alpha6 beta1 mediates retinal ganglion cell neurite outgrowth and compensates for the absence of alpha3 beta1. Finally, we show that key features of the retinal neuron response to LN-1 also characterize neurons of the hippocampus, thalamus, and cerebral cortex; these include poor response to untreated LN-1, extensive neurite outgrowth on antibody-activated LN-1 or on fragment E8, and dependence of this response on integrin alpha6 beta1 and at least one other long arm-binding beta1 integrin. These data suggest that regulation of LN-1 function via the process of activation could have important consequences for axonal regeneration. Curiously, the data also imply that the mechanism of laminin activation involves enhanced function at sites that cannot be considered cryptic.

Animals↗
PubMed2003

Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration.

Netrins, axon guidance cues in the CNS, have also been detected in epithelial tissues. In this study, using the embryonic pancreas as a model system, we show that Netrin-1 is expressed in a discrete population of epithelial cells, localizes to basal membranes, and specifically associates with elements of the extracellular matrix. We demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of CK19+/PDX1+ putative pancreatic progenitors on Netrin-1. These results provide evidence for the activation of epithelial cell adhesion and migration by a neural chemoattractant, and identify Netrin-1/integrin interactions as adhesive/guidance cues for epithelial cells.

Animals↗
PubMed2002

Laminin 10/11: an alternative adhesive ligand for epidermal keratinocytes with a functional role in promoting proliferation and migration.

We have investigated the expression and function of the isoforms of laminin bearing the alpha5 chain, i.e. laminin-10/11 in neonatal and adult human skin. By immunostaining human skin derived from a variety of anatomic sites, we found that the laminin-alpha5 chain is expressed abundantly in the basement membrane underlying the interfollicular epidermis and the blood vessels in the dermis. Interestingly, while the expression level of the well-studied laminin-5 isoform did not change significantly with age, laminin-10/11 (alpha5 chain) appeared to decrease in the basement membrane underlying the epidermis, in adult skin. In contrast, the levels of laminin-10/11 in the basement membrane underlying blood vessels remained unchanged in neonatal vs. adult skin. Importantly, in vitro cell adhesion assays demonstrated that laminin-10/11 is a potent adhesive substrate for both neonatal and adult keratinocytes and that this adhesion is mediated by the alpha3beta1 and alpha6beta4 integrins. Adhesion assays performed with fractionated basal keratinocytes showed that stem cells, transit amplifying cells and early differentiating cells all adhere to purified laminin-10/11 via these receptors. Further, laminin-10/11 provided a proliferative signal for neonatal foreskin keratinocytes, adult breast skin keratinocytes, and even a human papillomavirus type-18 transformed tumorigenic keratinocyte cell line in vitro. Finally, laminin-10/11 was shown to stimulate keratinocyte migration in an in vitro wound healing assay. These results provide strong evidence for a functional role for laminin-10/11 in epidermal proliferation during homeostasis, wound healing and neoplasia.

Adult↗
PubMed2002

Complex interactions between the laminin alpha 4 subunit and integrins regulate endothelial cell behavior in vitro and angiogenesis in vivo.

The alpha4 laminin subunit is a component of the basement membrane of blood vessels where it codistributes with the integrins alphavbeta3, alpha3beta1, and alpha6beta1. An antibody against the G domain (residues 919-1207; G(919-1207)) of the alpha4 laminin subunit inhibits angiogenesis in a mouse-human chimeric model, indicating the functional importance of this domain. Additional support for the latter derives from the ability of recombinant G(919-1207) to support endothelial cell adhesion. In particular, endothelial cell adhesion to G(919-1207) is half-maximal at 1.4 nM, whereas residues 919-1018 and 1016-1207 of the G domain are poor cellular ligands. Function blocking antibodies against integrins alphavbeta3 and beta1 and a combination of antibodies against alpha3 and alpha6 integrin subunits inhibit endothelial cell attachment to G(919-1207). Moreover, both alphavbeta3 and alpha3beta1 integrin bind with high affinity to G(919-1207). Together, our studies demonstrate that the G domain of laminin alpha4 chain is a specific, high affinity ligand for the alphavbeta3 and alpha3beta1 integrin heterodimers and that these integrins, together with alpha6beta1, function cooperatively to mediate endothelial cell-alpha4 laminin interaction and hence blood vessel development. We propose a model based on these data that reconcile apparent discrepancies in the recent literature with regard to the role of the alphavbeta3 integrin in angiogenesis.

Antibodies, Monoclonal↗
PubMed1999

Embryonic neurons adapt to the inhibitory proteoglycan aggrecan by increasing integrin expression.

The primary mediators of cell migration during development, wound healing and metastasis, are receptors of the integrin family. In the developing and regenerating nervous system, chondroitin sulfate proteoglycans (CSPGs) inhibit the integrin-dependent migration of neuronal growth cones. Here we report that embryonic sensory neurons cultured on the growth-promoting molecule laminin in combination with the inhibitory CSPG aggrecan rapidly adapt to inhibition. Adaptation is associated with a two- to threefold increase in the levels of RNA and surface protein for two laminin receptors, integrin alpha6beta1 and alpha3beta1, indicating that integrin expression is regulated by aggrecan. Increased integrin expression is associated both with increases in neuronal cell adhesion/outgrowth and with decreases in the ability of aggrecan to inhibit cell adhesion. Directly increasing integrin expression by adenoviral infection is sufficient to eliminate the inhibitory effects of aggrecan, indicating that upregulation of integrin receptors may promote neuronal regeneration in the presence of inhibitory matrix components.

Aggrecans↗
PubMed1997

Coordinated expression of integrin alpha6beta1 and laminin in hepatocellular carcinoma.

The interaction between tumor cells and laminin mediated by laminin-binding integrins is critical for tumor invasion and metastasis. The aim of this study was to clarify the altered expression of laminin-binding integrins with the change of laminin deposition in hepatocellular carcinoma (HCC) in comparison with cirrhotic or normal liver by immunohistochemistry. In HCC, hepatoma cells and sinusoidal endothelial cells expressed integrins alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta1. Integrins alpha1beta1 and alpha6beta1 were detected in a continuous pattern along the sinusoids in accordance with laminin assembly. Integrins alpha2beta1 and alpha3beta1 were detected in a discontinuous pattern at these sites. Integrin alpha6beta4 was not detected. In cirrhotic liver, although integrins alpha1beta1 and alpha6beta1 as well as laminin were detected in a continuous pattern along the sinusoids, integrins alpha2beta1, alpha3beta1, and alpha6beta4 were not detected. In normal liver, although integrin alpha1beta1 was detected in a continuous pattern along the sinusoids, neither integrins alpha2beta1, alpha3beta1, alpha6beta1, alpha6beta4, nor laminin were detected. We have clarified that, of laminin-binding integrins, the localization of integrin alpha6beta1 shows the best correspondence with the localization of laminin. These results suggest that of laminin-binding integrins, integrin alpha6beta1 is very important for cell-laminin interactions in HCC.

Adult↗
PubMed1997

Modulation of myoepithelial-associated alpha6beta4 integrin in a breast cancer cell line alters invasive potential.

In normal breast, cell-stromal contact is mediated by myoepithelial cells which strongly express alpha2beta1, alpha3beta1, and alpha6beta4 integrins, while epithelial cells exhibit alpha2beta1 and alpha3beta1 integrins at cell-cell borders, but do not express alpha6beta4 integrin. Breast carcinomas consistently show down-regulation of all integrins. We have investigated the modulatory effect of stromal proteins, hormones, and transforming growth factor beta (TGF-beta) on integrin expression in breast cancer cell lines MCF-7, T47-D, and MDA-MB 231 using indirect immunofluorescence and confocal laser scanning microscopy. MCF-7 and T47-D cells displayed low levels of both alpha2beta1 and alpha3beta1 integrins, and no alpha6beta4 integrin, and this profile remained unchanged by modulatory agents. The MDA-MB 231 cells exhibited stronger staining for alpha2beta1 and alpha3beta1 integrins and focal staining for alpha6beta4 integrin under control conditions, but markedly enhanced reactivity for the alpha6beta4 complex in the presence of TGF-beta. This was associated with acquisition of a spread cellular morphology and localization of alpha6beta4 at the cell periphery in a discrete punctate distribution. There was associated enhanced expression of epiligrin, the ligand for alpha6beta4, with similar localization to the cell periphery. Cell invasion assays through a Matrigel barrier revealed significantly reduced invasive potential of TGF-beta-treated cells, an effect largely reversed following preincubation of the treated cells with anti-beta4 integrin antibody. We conclude that alpha6beta4 integrin can be up-regulated by TGF-beta and has an anti-invasive effect on MDA-MB 231 cells. In addition to alpha6beta4, MDA-MB 231 cells exhibit other myoepithelial markers including cytokeratin 14, vimentin, and weak expression of CALLA. These findings support the concept of a subgroup of breast carcinomas displaying features of myoepithelial differentiation.

Antigens, Surface↗