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Results for “Integrin alpha3”

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At least 361 records · Page 20Linked to original sources

PubMed2006

Paxillin phosphorylation and integrin expression in osteoblasts infected by Porphyromonas gingivalis.

OBJECTIVE: We investigated early biological events initiated by Porphyromonas gingivalis infection of human osteoblasts, focusing on tyrosine-phosphorylation and the expression of key components in focal adhesion and cell signalling. DESIGN: Human primary osteoblasts were challenged for 1h with Porphyromonas gingivalis. Tyrosine-phosphorylation of paxillin and focal adhesion kinase (FAK) was examined by Western blotting. Changes in alpha3- and beta1-integrin mRNA expression were quantified by RT-PCR. RESULTS: Tyrosine-phosphorylation of paxillin was proportional to the size of the Porphyromonas gingivalis inoculum. FAK, a potential kinase for paxillin, was not activated. The amount of alpha3- and beta1-integrins, determined by Western blotting, did not vary significantly, while the corresponding mRNA levels fell significantly when a large bacterial inoculum was used. CONCLUSIONS: These results indicate that Porphyromonas gingivalis infection of osteoblasts in vitro triggers tyrosine-phosphorylation of paxillin but not FAK and modify alpha3- and beta1-integrin mRNA expression. This infection thus appears to have different effects on components with essential roles in focal adhesion (paxillin) and cell signalling (FAK and integrins).

Bacterial Adhesion↗

PubMed2001

Significance of integrin alpha2/beta1 in peritoneal dissemination of a human gastric cancer xenograft model.

In the present study, the role of integrin alpha2/beta1 in peritoneal dissemination of gastric cancer was investigated using an in vivo xenograft model for the highly metastatic MKN-45-P gastric cancer cells. Metastatic ability of MKN-45-P cells was significantly associated with the simultaneous expression of integrin alpha2 and alpha3 subunits. In an in vitro adhesion assay, neutralizing antibody for integrin alpha2 or beta1 subunit inhibited the adhesion of MKN-45-P cells to collagen type I and type IV. Moreover, the injection of anti-beta1 monoclonal antibody reduced the number of cancer cells on the peritoneum in nude mice that had been inoculated with MKN-45-P cells. These results suggest that integrin alpha2/beta1 represents a candidate target molecule available for the prevention of gastric cancer peritoneal dissemination.

Adenocarcinoma↗

PubMed1997

Spatial and temporal analyses of integrin and Muc-1 expression in porcine uterine epithelium and trophectoderm in vitro.

The expression of the glycoproteins Muc-1 and integrin subunits (alpha1, alpha3, alpha4, alpha5, alpha(v), beta1, and beta3), all of which may be involved in the control of uterine receptivity, was examined in cultured porcine uterine epithelial (pUE) cells. Integrin subunit expression was also determined in trophoblastic vesicles generated from Day 12 and Day 15 pig conceptuses. Immunocytochemistry was performed on pUE cells cultured on several substrates (glass, serum, fibronectin, or Matrigel) in DME/F12 medium with 5% charcoal/dextran-stripped fetal bovine serum either containing no steroids or supplemented with estrogen, progesterone, or estrogen plus progesterone, or in medium with 5% complete fetal bovine serum. In addition, pUE cells were grown on Matrigel-coated Millicell filter inserts to facilitate development of structurally and functionally distinct apical and basal domains (i.e., polarized pUE cells) and were maintained in the same medium with supplements. The major findings in this investigation are that 1) Muc-1 and alpha1, alpha3, alpha4, alpha5, alpha(v), beta1, and beta3 integrin subunits are expressed on pUE cells in vitro; 2) Muc-1 and several integrin subunits are modulated by steroid hormones if culture conditions are provided that permit development of cell polarity; 3) the expression and steroid-induced modulation of Muc-1 and several integrin subunits in polarized pUE cells are similar to those detected in vivo; and 4) the expression of alpha1, alpha3, alpha4, alpha5, alpha(v), beta1, and beta3 integrin subunits by trophoblastic vesicles is identical to their expression on trophectoderm of intact conceptuses in vivo. These results suggest that the properties of polarized pUE cells and trophoblastic vesicles are comparable to those of their counterparts in vivo and are, therefore, useful as in vitro model systems to study conceptus-endometrial interactions during the periimplantation period and the control of uterine receptivity to implantation.

Animals↗

PubMed2002

Melanoma cell attachment, invasion, and integrin expression is upregulated by tumor necrosis factor alpha and suppressed by alpha melanocyte stimulating hormone.

We have previously shown alpha-melanocyte stimulating hormone to protect melanocytes and melanoma cells from the proinflammatory actions of tumor necrosis factor-alpha. The aim of the study was to extend this work to look into the influence of tumor necrosis factor-alpha on melanoma cell attachment, invasion, and integrin expression and ask to what extent alpha-melanocyte stimulating hormone might protect cells from tumor necrosis factor-alpha stimulation of increased integrin expression. HBL human melanoma cells were studied under resting and stressed conditions using tumor necrosis factor-alpha as a proinflammatory cytokine. Functional information on the actions of tumor necrosis factor-alpha on melanoma cells was obtained by examining the strength of attachment of melanoma cells to substrates and the ability of melanoma cells to invade through fibronectin. alpha3, alpha4, and beta1 integrin expression was detected by Western immunoblotting and the ability of alpha-melanocyte stimulating hormone to oppose the actions of tumor necrosis factor-alpha was studied on HBL cell attachment, invasion, and integrin subunit expression. Our results show that tumor necrosis factor-alpha increases the number of melanoma cells attaching to collagen (types I and IV) and tissue culture polystyrene, increases ability to invade through fibronectin, and upregulates the expression of alpha3 (28%), alpha4 (90%), and beta1 (65%) integrin subunit expression. In contrast, alpha-melanocyte stimulating hormone reduced cell attachment, invasion, and integrin expression and opposed the stimulatory effects of tumor necrosis factor-alpha. In conclusion this study provides further evidence of alpha-melanocyte stimulating hormone acting to "protect" melanoma cells from proinflammatory cytokine action. Our data support a hypothesis that an inflammatory environment would promote melanoma invasion and that the anti-invasive actions of alpha-melanocyte stimulating hormone are consistent with its working in an anti-inflammatory capacity.

Antineoplastic Agents↗

PubMed1996

Adhesive and migratory behaviors of nevus cells differ from those of epidermal melanocytes and are not linked to the histological type of nevus.

It has been postulated that acquired nevi undergo life span continuous evolution from junctional, presumably in radial expanding phase at the dermal epidermal junction, to compound and then to dermal nested nevi. In an attempt to correlate the morphology of nevi with biological data, we have investigated whether migratory and adhesive phenotypes of nevus cells could account for histological patterns and possible spatiotemporal changes in nevi. Nevus cells were cultured from compound and dermal nevi and compared to normal epidermal cultured melanocytes from children and adults. AR nevus cells showed similar in vitro adhesive and migratory indexes on laminin-1, laminin-5/nicein, fibronectin, or collagen IV substrates, suggesting that these intrinsic characteristics do not account for the tendency to dermal nesting and/or to radial growth along the dermal-epidermal junction. The cells from epidermal and dermal parts of compound nevi migrated similarly across a reconstituted basement membrane. The results show that intrinsic adhesive and migratory behaviors of nevus cells were not associated with a histological type of nevus. Interestingly, differences in migratory phenotype and intercellular adhesion capacities between nevus cells and normal melanocytes indicated that they could represent different melanocytic cell subpopulations. Finally, melanocytes from adults and children expressed similar levels of the same integrins as all nevus cells but showed differences in function of both alpha3 and alpha6 integrin subunits and in migratory/adhesive behaviors, which may suggest different states of melanocyte maturation.

Adult↗

PubMed2002

Defects in keratinocyte activation during wound healing in the syndecan-1-deficient mouse.

Mice lacking syndecan-1 are viable, fertile and have morphologically normal skin, hair and ocular surface epithelia. While studying the response of these mice to corneal epithelial and skin wounding, we identified defects in epithelial cell proliferation and regulation of integrin expression. mRNA profiling of corneal epithelial tissues obtained from wild-type and syndecan-1(-/-) mice suggest that these defects result from differences in overall gene transcription. In the cornea, syndecan-1(-/-) epithelial cells migrate more slowly, show reduced localization of alpha9 integrin during closure of wounds and fail to increase their proliferation rate 24 hours after wounding. In the skin, we did not document a migration defect after full thickness wounds but did observe cell proliferation delays and reduced localization of alpha9 integrin in the syndecan-1(-/-) epidermis after dermabrasion. Despite increased cell proliferation rates in the uninjured syndecan-1(-/-) epidermis and the corneal epithelium, morphologically normal epithelial thickness is maintained prior to injury; however, wounding is accompanied by prolonged hypoplasia in both tissues. Analyses of integrin protein levels in extracts from full thickness skin, revealed increased levels of alpha3 and alpha9 integrins both prior to injury and after hair removal in syndecan-1(-/-) mice but no increase 2 days after dermabrasion. These data for the first time show involvement of alpha9 integrin in skin wound healing and demonstrate essential roles for syndecan-1 in mediating cell proliferation and regulation of integrin expression in normal and wounded epithelial tissues.

Animals↗

PubMed1998

Histo-blood group A/B antigen deletion/reduction vs. continuous expression in human tumor cells as correlated with their malignancy.

Deletion or reduction of histo-blood group A or B antigen in tumors of A or B individuals is clearly correlated with the degree of malignancy and metastatic potential in many types of human cancer. Haptotactic motility of A+H- or B+H- colonic or gastric tumor cell lines produced by transfection of A or B gene was significantly lower than that of parental A-H+ or B-H+ cells. This is ascribable to reduced function of alpha3 or alpha6/beta1 integrin receptor as we have recently shown. However, phenotypic changes resulting from gene transfection may not reflect physiological states associated with deletion or reduction vs. continuous expression of A or B antigen in tumors. We now describe the separation and phenotype characterization of A- cells from A+ tumor cell lines derived originally from colonic tumors of patients with histo-blood group A. A+ and A- populations were detected in originally A+ tumor cell lines SW480 and HT29. A- separated from A+ populations isolated from SW480 and HT29 were characterized by greatly enhanced haptotactic motility associated with reduced or deleted A expression at alpha3, alpha6, and beta1 integrin receptors which control cell motility. Nevertheless, expression of integrin receptors at the surface of A populations is the same as that for A+ populations for both SW480 and HT29 cells. Thus, A vs. H glycosylation in integrin receptors may alter their haptotactic function. Cell proliferation as reflected by 3H-thymidine incorporation was also reduced significantly in A+ as compared to A- populations. Our findings indicate that the degree of haptotactic motility and proliferation of colonic tumor cells are physiologically associated with the deletion or reduction vs. continuous expression of the histo-blood group A antigen.

ABO Blood-Group System↗

PubMed2005

Laminin-5 with transforming growth factor-beta1 induces epithelial to mesenchymal transition in hepatocellular carcinoma.

BACKGROUND & AIMS: How hepatocellular carcinoma (HCC) cells acquire the ability to invade surrounding tissue is unknown, but epithelial mesenchymal transition (EMT) likely plays a role. We investigate how transforming growth factor (TGF)-beta1 and extracellular matrix protein Laminin-5 (Ln-5) induce EMT and cancer invasion. METHODS: Snail, Slug, E-cadherin, beta-catenin and Ln-5 were investigated on HCC tissues and on HCC cell lines. RESULTS: We show that in HCC but not in peritumoral tissue of the same HCC patients, Ln-5, Snail, and Slug are up-regulated, E-cadherin is down-regulated and beta-catenin is translocated into the nuclei. In vitro, HCC "invasive" cells, partially EMT-transformed, show low levels of E-cadherin. In presence of Ln-5, Snail, and Slug are up-regulated, E-cadherin is down-regulated, beta-catenin is translocated into the nuclei, and cells undergo a dramatic morphological change, becoming scattered and undergoing a complete EMT. This effect is reversed by anti-alpha3 but not by anti-alpha6 integrin blocking antibody. HCC "noninvasive" cells are not EMT-transformed, and have constitutively high levels of E-cadherin. In presence of Ln-5, cells undergo partial EMT, Snail, and Slug are up-regulated, E-cadherin is down-regulated but cells do not scatter. However, the presence of both Ln-5 and TGF-beta1 completes the EMT process, beta-catenin is translocated into the nuclei, cells scatter and become invasive, recalling the "invasive" cells. In this case, too, the effect is reversed by anti-alpha3 integrin blocking antibody. CONCLUSIONS: Our study shows that Ln-5 and TGF-beta1 cooperatively induce EMT in HCC, suggesting the microenvironment as a potential target for new biological therapies.

Cadherins↗

PubMed2003

Membrane type-1 matrix metalloproteinase (MT1-MMP) processing of pro-alphav integrin regulates cross-talk between alphavbeta3 and alpha2beta1 integrins in breast carcinoma cells.

We have recently demonstrated that in breast carcinoma MCF7 cells MT1-MMP processes the alphav, alpha3, and alpha5 integrin precursors generating the respective mature S-S-linked heavy and light alpha-chains. The precursor of alpha2 integrin subunit was found resistant to MT1-MMP proteolysis. The processing of the alphav subunit by MT1-MMP facilitated alphavbeta3-dependent adhesion, activation of FAK signaling pathway, and migration of MCF7 cells on vitronectin. To elucidate further the effects of MT1-MMP on cellular integrins, we examined the functional activity of alpha5beta1 and alpha2beta1 integrins in MCF7 cells expressing MT1-MMP. Either expression of MT1-MMP alone or its coexpression with alphavbeta3 failed to affect the functionality of alpha5beta1 integrin, and adhesion of cells to fibronectin. MT1-MMP, however, profoundly affected the cross-talk involving alphavbeta3 and alpha2beta1 integrins. In MT1-MMP-deficient cells, integrin alphavbeta3 suppressed the functional activity of the collagen-binding alpha2beta1 integrin receptor and diminished cell adhesion to type I collagen. Coexpression of MT1-MMP with integrin alphavbeta3 restored the functionality of alpha2beta1 integrin and, consequently, the ability of MCF7 cells to adhere efficiently to collagen. We conclude that the MT1-MMP-controlled cross-talk between alphavbeta3 and alpha2beta1 integrins supports binding of aggressive, MT1-MMP-, and alphavbeta3 integrin-expressing malignant cells on type I collagen, the most common substratum of the extracellular matrix.

Breast Neoplasms↗

PubMed1997

alphaV Integrins on HT-29 colon carcinoma cells: adhesion to fibronectin is mediated solely by small amounts of alphaVbeta6, and alphaVbeta5 is codistributed with actin fibers.

HT-29 colon carcinoma cells form liver metastases upon intrasplenic injection, and adhesion to fibronectin under the liver microvascular liver endothelium is likely to be important for metastasis formation. We have therefore studied the integrins involved in fibronectin adhesion. This was not affected by blocking antibodies against the beta1, alpha3, and alpha5 integrin subunits, but it was blocked by an RGD-containing peptide, indicating involvement of RGD-dependent non-beta1 alphaV integrins. Both alphaVbeta5 and alphaVbeta6 were detected on HT-29 cells. Blocking mAb against alphaV, but not against alphaVbeta5, abolished adhesion. From a HT-29 cell lysate, only alphaVbeta6 bound to a fibronectin-Sepharose column. Thus, alphaVbeta6 is the main fibronectin receptor on HT-29 cells, despite the very low levels of alphaVbeta6 and the much higher levels of alphaVbeta5. The HT29 cells did not spread on fibronectin in the absence of serum, not even after a three- to fourfold increase in alphaVbeta6 levels, induced by interleukin 4. The cells did spread on vitronectin. Using immunofluorescence we observed that both on vitronectin and on fibronectin alphaVbeta5 was arranged in a striped pattern, aligned with actin fibers, and not in focal adhesions. On fibronectin, but not on vitronectin, alphaVbeta6 was concentrated in a punctate pattern at the periphery of cell islands.

Actins↗

PubMed2004

Motility response to insulin-like growth factor-I (IGF-I) in MCF-7 cells is associated with IRS-2 activation and integrin expression.

In MCF-7L cells, insulin-like growth factor-I (IGF-I) stimulates activation of insulin receptor substrate-1 (IRS-1) and enhances cell proliferation. While others have shown that IGF-I enhances cell motility in MCF-7 cells, we have not been able to demonstrate this. To determine if the source of MCF-7 cells account for these reported differences, we examined the MCF-7 cells available from the American Type Culture Collection (MCF-7/ATCC) and compared them to the MCF-7L cells maintained in our laboratory. Both MCF-7L and MCF-7/ATCC grew in response to 5 nM IGF-I and 1 nM estradiol. However, only MCF-7/ATCC demonstrated IGF-I stimulated motility. Immunoprecipitation of IRS substrates followed by anti-phosphotyrosine blotting demonstrated that both IRS-1 and IRS-2 were activated by IGF-I in these cells. However, MCF-7/ATCC cells had greater phosphorylation of IRS-2 compared to MCF-7L. Immunoblots showed that levels of IRS-1 and IRS-2 were comparable between cell lines. We have previously shown that fibronectin-binding integrins are necessary for IGF-stimulated motility. Similar levels of beta1 integrin were detected in both strains of MCF-7. However, low levels of alpha5 and alpha3 were detected in MCF-7L cells whereas high levels of alpha3 and alpha5 integrin were expressed in MCF-7/ATCC cells. Inhibition of integrin function by a blocking antibody or inhibitory peptide diminished IGF-mediated motility in MCF-7/ATCC. In MCF-7/ATCC cells, IGF-I stimulation was associated with a movement of IRS-2 to the leading edge of filopodia. Thus, patterns of integrin expression among breast cancer cell lines may partially explain the different motility behavior of cells in response to IGF-I. IRS-2 activation and integrin occupancy are both required for IGF-stimulated motility.

Breast Neoplasms↗

PubMed2002

Integrins and extracellular matrix proteins in the human childhood and adolescent growth plate.

Interaction of chondrocytes with the surrounding matrix significantly influences differentiation and growth. These processes involve cell surface proteins, particularly integrins. The aim of this study was to compare the expression of integrins (alpha1, alpha2, alpha3, alpha5, alpha6, alphav, beta1, beta3, and beta5 subunits) together with matching binding proteins in human childhood and adolescent growth plate cartilage using immunohistochemistry. Integrin beta1 was detected in all chondrocytes of the growth plate cartilage, beta3 only in osteoclasts of the opening zone, and beta5 in hypertrophic chondrocytes and osteoblasts. Integrin alpha1, alpha2, and alpha5 subunits were expressed by chondrocytes in the proliferative and hypertrophic zone as well as in osteoblasts and osteoclasts. Integrin av and alpha6 subunits were present in chondrocytes of all zones, alpha3 only in osteoclasts. Collagen type II and fibronectin were seen throughout the growth plate, collagen type X in the hypertrophic zone, collagen type I in the ossifying trabecules. Laminin was expressed by chondrocytes in the resting zone and more weakly in the proliferative zone, collagen VI was present in the pericellular and interterritorial matrix in all zones of the growth plate. These results differ from previous reports on the distribution of integrins in the fetal growth plate. However, there was no difference in integrin expression in children before and during puberty. Our results indicate that integrin expression is not influenced by endocrine factors during sexual maturation and suggest that the process of skeletal maturation is not regulated via altered integrin expression.

Adolescent↗

PubMed1999

Laminin 5 promotes activation and apoptosis of the T cells expressing alpha3beta1 integrin.

By introducing an alpha3 gene-containing plasmid into a human T cell line Jurkat, we prepared the T cells, which express a high level of the alpha3beta1 integrin, to assess the role of laminin 5 in the skin immune system. The alpha3beta1-expressing T cells adhered to laminin 5 and exhibited spreading. These adhered T cells showed a significant tyrosine phosphorylation of intracellular proteins including p59(fyn) upon T-cell receptor (TCR) stimulation. Six hours after cross-linking TCR, these cells on laminin 5 secreted a three times higher level of IL-2 than those on a BSA-coated plate. Twenty hours after the stimulation, 48% of the alpha3beta1-expressing T cells on laminin 5 caused apoptosis. The protein level of cyclin D3 and E decreased, while that of p53 increased in these T cells. These data suggest that laminin 5 may play at least two regulatory roles for T cell functions: augmentation of IL-2 production by antigen-stimulated T cells and induction of apoptosis in these T cells.

Apoptosis↗

PubMed2003

Beta1 integrin/focal adhesion kinase-mediated signaling induces intercellular adhesion molecule 1 and receptor activator of nuclear factor kappaB ligand on osteoblasts and osteoclast maturation.

We have assessed characteristics of primary human osteoblasts, shedding light on signaling mediated by beta1 integrin. beta1 integrins are major receptors for these matrix glycoproteins. 1) Integrins beta1, alpha2, alpha3, alpha4, alpha5, alpha6, and alphav were highly expressed on primary osteoblasts. 2) Engagement of beta1 integrins on osteoblasts by cross-linking with specific antibody or ligand matrices, such as fibronectin or collagen, augmented expression of intercellular adhesion molecule 1 (ICAM-1) and receptor activator of nuclear factor kappaB ligand (RANKL) on the surface. 3) Up-regulation of ICAM-1 and RANKL on osteoblasts by beta1 stimulation was completely abrogated by pretreatment with herbimycin A and genistein, tyrosine kinase inhibitors, or transfection of dominant negative truncations of focal adhesion kinase (FAK). 4) Engagement of beta1 integrins on osteoblasts induced tartrate-resistant acid phosphatase-positive multinuclear cell formation in the coculture system of osteoblasts and peripheral monocytes. 5) Up-regulation of tartrate-resistant acid phosphatase-positive multinuclear cell formation by beta1 stimulation was completely abrogated by transfection of dominant negative truncations of FAK. Our results indicate that beta1 integrin-dependent adhesion of osteoblasts to bone matrices induces ICAM-1 and RANKL expression and osteoclast formation via tyrosine kinase, especially FAK. We here propose that beta1 integrin/FAK-mediated signaling on osteoblasts could be involved in ICAM-1- and RANKL-dependent osteoclast maturation.

Antibodies, Monoclonal↗

PubMed1997

There is temporal and spatial expression of alpha1 (IV), alpha2 (IV), alpha5 (IV), alpha6 (IV) collagen chains and beta1 integrins during the development of the basal lamina in an "in vitro" skin model.

Temporal and spatial expression of alpha1 (IV), alpha2 (IV), alpha3 (IV), alpha4 (IV), alpha5 (IV), and alpha6 (IV) collagen chains was studied during the formation of the basal lamina in an "in vitro" skin model. A sequential study was performed at 7-d and 14-d cultures (lamina densa absent) and at 28-, 36-, and 56-d cultures (lamina densa present). Expression of beta1, beta4, alpha1, alpha2, alpha3, alpha5, alpha6 integrin subunits and co-localization with collagen IV was studied by regular and laser confocal indirect immunofluorescence microscopy. mRNA expression of alpha2 (IV) and alpha6 (IV) chains was estimated by northern blots. The earliest expression of alpha1 (IV) and alpha2 (IV) collagen chains was noted in 7-d cultures restricted to basal keratinocytes. At 14-d cultures, alpha1 (IV) and alpha2 (IV) chains were noted in basal keratinocytes and as a broad band (10 microm) in the adjacent dermis. At this stage 80% of the alpha2 (IV) mRNA was expressed in the dermis and 20% in the epidermis. At 28-, 36-, and 56-d cultures the alpha1 (IV) and alpha2 (IV) chains were present in a linear distribution at the epidermo-dermal junction and in the upper dermis. The alpha6 (IV) collagen chains were expressed much later at 36-d cultures and the alpha5 (IV) at 56 d, both mostly in a linear distribution but also in the adjacent dermis. Alpha6 (IV) mRNA was demonstrated in the dermis of 36-d cultures. There was co-localization of collagen IV and beta1 integrin subunits in 14-d cultures at the matrix site of keratinocytes. Functional perturbation studies with AIIB2 monoclonal antibody (anti-beta1 subunits) and competitive inhibition with a collagen cyanogen bromide digestion derived fragment (CB3[IV]) that contains the collagen IV ligand for alpha1beta1, alpha2beta1 integrins, altered the pattern of collagen IV deposition.

Antibodies, Monoclonal↗

PubMed2000

Expression of beta1-integrins and N-cadherin in bladder cancer and melanoma cell lines.

Changes in the expression of integrins and cadherins might contribute to the progression, invasion and metastasis of transitional cell cancer of the bladder and of melanomas. The expression of alpha5 (P < 0.001), alpha2 and beta1 (P < 0.05 - P < 0.001) integrin subunits in melanoma cells from noncutaneous metastatic sites (WM9, A375) were significantly increased as compared to cutaneous primary tumor (WM35) and metastatic (WM239) cell lines. These differences might be ascribed to the invasive character of melanoma cells and their metastasis to the noncutaneous locations. The significantly heterogeneous expression of beta1 integrin subunit in two malignant bladder cancer cell lines (T24 and Hu456) and nonsignificant differences in the expression of alpha2, alpha3, and alpha5 subunits between malignant and non-malignant human bladder cell lines do not allow an unanimous conclusion on the role of these intergrin subunits in the progression of transitional cancer of bladder. The adhesion molecule, expressed in all studied melanoma and bladder cell lines, that reacted with anti-Pan cadherin monoclonal antibodies was identified as N-cadherin except in the HCV29 non-malignant ureter cell line. However, neither this nor any other bladder or melanoma cell line expressed E-cadherin. The obtained results imply that the replacement of E-cadherin by N-cadherin accompanied by a simultaneous increase in expression of alpha2, alpha3 and alpha5 integrin subunits clearly indicates an increase of invasiveness of melanoma and, to a lesser extent, of transitional cell cancer of bladder. High expression of N-cadherin and alpha5 integrin subunit seems to be associated with the most invasive melanoma phenotype.

Antibodies, Monoclonal↗

PubMed2006

Wound healing is defective in mice lacking tetraspanin CD151.

The tetraspanin CD151 forms complexes in epithelial cell membranes with laminin-binding integrins alpha6beta4, alpha3beta1, and alpha6beta1, and modifies integrin-mediated cell migration in vitro. We demonstrate in this study that CD151 expression is upregulated in a distinct temporal and spatial pattern during wound healing, particularly in the migrating epidermal tongue at the wound edge, suggesting a role for CD151 in keratinocyte migration. We show that healing is significantly impaired in CD151-null mice, with wounds gaping wider at 7 days post-injury. The rate of re-epithelialization of the CD151-null wounds is adversely affected, with significantly less wound area being covered by migrating epidermal cells. Our studies reveal that although laminin levels are similar in wild-type and CD151-null wounds, the organization of the laminin in the basement membrane is impaired. Furthermore, upregulation of alpha6 and beta4 integrin expression is adversely affected in CD151-null mice wounds. In contrast, we find no significant effect of CD151 gene knockout on alpha3 and beta1 integrin expression in wound repair. We suggest that mice lacking the CD151 gene are defective in wound healing, primarily owing to impairment of the re-epithelialization process. This may be due to defective basement membrane formation and epithelial cell adhesion and migration.

Animals↗

PubMed2001

Inhibition of lens epithelial cell adhesion by the calcium antagonist Mibefradil correlates with impaired integrin distribution and organization of the cytoskeleton.

BACKGROUND: Posterior capsule opacification is the most common complication of primary cataract surgery and is caused by migration and proliferation of residual lens epithelial cells onto the posterior capsule. Interfering with the mechanisms involved in cell adhesion is a suitable approach to prevent posterior capsule opacification. METHODS: Mibefradil, a T-type calcium-channel blocker, was used to examine the influence on adhesion-mediating mechanisms in human lens epithelial cells derived from cataract surgery. Adhesion was evaluated by light microscopy on the anterior capsules. Expression of integrin receptors was studied by flow cytometry. The influence on the distribution of integrin receptors on the cell surface and the organization of the cytoskeleton was examined by immunofluorescence using a confocal microscope. RESULTS: The calcium-channel blocker Mibefradil inhibited cell adhesion on the anterior capsule wall at concentrations between 10 and 100 pNM. The cells expressed the integrin subunits beta1 and alpha3. Mibefradil distinctly impaired the distribution of these integrins on the cell surface in culture. The cells express the cytoskeletal components actin, vimentin and, very weakly, cytokeratin. The structural organization of the actin filaments and vimentin was strongly disrupted with pronounced fragmentation of the actin filaments in the presence of the calcium-channel blocker. CONCLUSION: The results suggest that the inhibition of cell adhesion by the calcium-channel blocker Mibefradil involves the impairment of integrin-mediated mechanisms. The use of this calcium antagonist appears to be a suitable therapeutic approach to prevent posterior capsule opacification.

Calcium Channel Blockers↗