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Results for “Integrin alpha6beta1”

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PubMed2000

alpha5 integrin distribution and TGFbeta1 gene expression in supraglottic carcinoma: their role in neoplastic local invasion and metastasis.

BACKGROUND: Head and neck carcinomas are characterized by tumor-infiltrating lymphocytes (TIL) producing cytokines. Adhesion molecules, extracellular matrix proteins (ECMPs), and cytokines regulate cell-cell and cell-ECMPs interactions. We investigated the distribution of these proteins to contribute to better understanding of their role in local tumor invasion and metastasis. METHODS: Distribution of integrins, laminin, type IV collagen, tenascin, and fibronectin was immunohistochemically evaluated in 13 supraglottis carcinomas. Cytokines gene expression was assessed by reverse-transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Neoplastic cells were alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1 and alpha6beta1 positive. Normal and metaplastic epithelium was alpha5beta1 negative; the stroma of primary and metastatic tumors was tenascin and fibronectin positive. TGFbeta1 and IFNgamma gene expression was observed in the majority of tumors. CONCLUSIONS: Because TGFbeta1 is known to down-modulate immune processes and to increase alpha2beta1, alpha5beta1, and tenascin distribution, we propose that their expression in neoplastic cells of supraglottis carcinoma might represent an immune-related process able to help tumor growth and progression.

Antigens, CD↗

PubMed1998

Integrin laminin receptor profile of pulmonary squamous cell and adenocarcinomas.

The differential expression of laminin receptors has been shown to modulate the invasive capability of malignant cells. We have investigated the reactivity of human pulmonary squamous carcinomas (SSC, n = 20) and adenocarcinomas (ADC, n = 20) with monoclonal antibodies to the cytoplasmic and extracellular domains of the integrin subunits alpha3 and alpha6. Integrins containing these subunits are laminin receptors. Monoclonal antibodies to beta1 and beta4 subunits, the beta1C splice variant of beta1, as well as to Ki-67, were also used. Reverse transcription polymerase chain reaction (PCR) single-strand conformational polymorphism analysis was done to detect possible mutations in the cytodomains. All carcinomas expressed alpha3 extensively; alpha3 expression predominated (40 of 40) over alpha6 (25 of 40). In all alpha6-positive carcinomas, alpha6A was expressed, whereas alpha6B was weakly expressed only in some of them. No mutations of the intracytoplasmic domain A of alpha3 and of the A or B intracytoplasmic domains of alpha6 were shown. Notably, in normal bronchial epithelium, alpha6 colocalized with beta4, whereas in the tumors, alpha6A frequently overlapped with beta1 in a circumferential pattern; alpha6beta1 coexpression was also shown by coprecipitation experiments. Strong and extensive beta4 reactions were invariably polarized at the cell/stroma interface in SCC and ADC. An inverse correlation was found between the expression of beta1C and Ki-67. The prevalence of alpha6A in pulmonary SCC and ADC is in contrast with previous results in colonic ADC in which alpha6B prevails, and alpha6 predominates over alpha3. The absence of mutations of the cytodomains suggests that the integrin subunits of these carcinomas are potentially active. Predominance of alpha3 over alpha6 and of alpha6A over alpha6B may contribute to explain the aggressive and metastatic behavior of lung carcinomas.

Adenocarcinoma↗

PubMed1997

Regulated expression of fibronectin, laminin and related integrin receptors during the early chondrocyte differentiation.

We have investigated the expression and localization of fibronectin, laminin, and their receptors, and we used an in vitro chick chondrocyte differentiation model to define a time hierarchy for their appearance in early chondro-genesis and to determine their role in the cell condensation process. By serum fibronectin depletion/reconstitution, or GRGDSP peptide competition experiments, we show that fibronectin contributes to the initial cell-cell interactions that occur during condensation. In later stages, a down-regulation of both fibronectin and of its alpha5beta1 integrin receptor occur, as demonstrated by mRNA and protein kinetics. Immunolocalisation studies suggest that the reduction of fibronectin in discrete areas is involved in local activation of the cell differentiation program. Furthermore, we show that laminin is expressed during the in vitro cell condensation process in areas that are negative for fibronectin staining. The types of laminin as well as the timing of expression have been determined by northern blot and RT-PCR analyses. The highest levels of expression are coincident with maximal cell aggregation. The alpha3beta1 laminin receptor, highly expressed in dedifferentiated cells, follows later on the ligand trend. During in vitro chondrogenesis, a down-regulation in the B isoform, and an up-regulation of the A isoform, of the alpha subunit of the alpha6beta1 laminin receptor occurs. Immunolocalisation studies suggest that laminin is involved in the definition of differentiating areas as opposed to non differentiating areas of the condensed region, i.e. the periphery, which eventually gives rise to the perichondrium.

Animals↗

PubMed1999

Expression of laminins and their integrin receptors in different conditions of synovial membrane and synovial membrane-like interface tissue.

OBJECTIVE: To demonstrate the expression of laminins (Lns) and their integrin (Int) receptors in different synovial samples and synovial membrane-like interface tissues from well fixed and aseptically loosened total hip replacement (THR), and the potential role of Ln-Int interaction in the production of collagenases and cytokines. METHODS: Immunohistochemical staining was done to detect the distribution of EHS Ln, Ln alpha2, alpha3, alpha5, beta1, beta2 chains and Int alpha1, alpha2, alpha3, alpha6, beta1, beta4 subunits in different samples. Double immunofluorescence labelling was used to find colocalisation of Int alpha6 subunit and collagenase-1/collagenase-3/TNFalpha/IL6. RESULTS: General Ln immunoreactivity was detected in all specimens. Ln alpha5, beta1 and beta2, but not alpha2 and alpha3 chains were seen in the synovial lining and the basement membrane of blood vessels with the intensity/extent of labelling in the following rank order: rheumatoid arthritis (RA) loosened prostheses, osteoarthritis, well fixed prostheses, traumatic knees. Among Int subunits, staining for beta1 was usually the strongest, followed by staining for Int alpha6, alpha1, alpha3, and alpha2 subunits, with the same rank order for overall expression of Lns. Int beta4 subunit was not detectable in most of the specimens. Double labelling focused on Int alpha6 subunit disclosed its frequent colocalisation with collagenases 1 and 3 and with tumour necrosis factor alpha and interleukin 6 in synovial lining. CONCLUSION: Synovial lining contains Ln-10, Ln-11, and Int alpha6beta1 and alpha1beta1 receptors. In aseptic loosening of THR, interface tissue has a similar Ln subtype and Int receptor composition as RA synovium, which confirms its "lining-like" phenotype. Synovial lining does not contain Ln-5 (alpha3beta3gamma2) or Int alpha6beta4, which are components of epithelial hemidesmosomes. The expression of Lns and their Int receptors is upregulated in inflammation. The close spatial relation between Ln and its Int receptors in synovial lining cells containing proteinases and cytokines suggests a potential role in joint destruction and prosthetic loosening.

Adult↗

PubMed1997

Dexamethasone inhibits prolonged survival and autocrine granulocyte-macrophage colony-stimulating factor production by human eosinophils cultured on laminin or tissue fibronectin.

BACKGROUND: Eosinophil autocrine generation of viability-promoting cytokines resulting from interaction with extracellular matrix (ECM) proteins may be important in promoting their persistence in allergic inflammation. OBJECTIVE: We examined eosinophil interaction with fibronectin, laminin, collagen, fibrinogen, hyaluronate, or vitronectin in terms of adhesion and for their ability to promote prolonged eosinophil survival by autocrine generation of IL-3, IL-5, or granulocyte-macrophage colony-stimulating factor (GM-CSF). The effect of dexamethasone was examined because it may inhibit integrin-dependent autocrine generation of viability-enhancing cytokines. METHODS: Microtiter wells were coated with different ECM proteins, and assays were performed to determine their levels of eosinophil adhesion, and tests were performed to determine their prolonged survival in culture. The receptors involved in these processes, the cytokines generated, and the effect of a dose range of dexamethasone were all examined. RESULTS: Eosinophils cultured for 3 days on laminin or tissue fibronectin exhibited dose-dependent prolonged survival, which was not seen with any other ECM protein. Unstimulated eosinophils adhered to wells coated with laminin or fibronectin but not to wells coated with any of the other ECM proteins that were tested. Laminin-dependent eosinophil adhesion and prolonged survival were inhibited by specific monoclonal antibodies to beta1 and alpha6beta1. Laminin-dependent survival was inhibited by a neutralizing antibody to GM-CSF, an anti-IL-5 antibody achieved a measurable but insignificant inhibition of survival, and an antibody to IL-3 had no effect. Increasing concentrations of dexamethasone (maximal at 10(-7) mol/L) inhibited both laminin- and fibronectin-dependent enhanced eosinophil viability at 3 days. Eosinophils cultured on either laminin or fibronectin for 24 or 72 hours generated picogram quantities of GM-CSF, which were inhibited by the addition of dexamethasone (10(-7) mol/L). CONCLUSION: We have confirmed that eosinophils adhere to laminin in an alpha6beta1-dependent manner, and this interaction results in the autocrine generation of GM-CSF, which enhances eosinophil survival in culture. Both laminin and tissue fibronectin-dependent autocrine GM-CSF generation were inhibited by physiologically relevant concentrations of dexamethasone. This may represent an important mechanism by which glucocorticoids reduce the tissue eosinophilia in allergic disease.

Anti-Inflammatory Agents↗