A Biochemical Characterization of the Binding of Osteopontin to Integrins αvβ1 and αvβ5

Hu, Dana D.; Lin, Emme C.K.; Kovach, Nicholas L.; Hoyer, John R.; Smith, Jeffrey W.

doi:10.1074/jbc.270.44.26232

Cited by 233 publications

(184 citation statements)

References 48 publications

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“…In addition, Osteopontin bind several different cellular receptors, potentially allowing it to stimulate various signalling pathways and influence cellular events that may ultimately promote tumorgenesis, adhesion, migration and metastasis (Hu et al, 1995;Liaw et al, 1995;Weber et al, 1996;Al-Shami et al, 2005). The down-stream Osteopontin signals which interrupt the cell cycle, prevent apoptosis and promote cell survival are integral to tumour progression (Evan and Vousden, 2001).…”

Section: Discussionmentioning

confidence: 99%

Expression of Osteopontin in oesophageal squamous cell carcinoma

et al. 2006

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Osteopontin is a multifunctional 34 kDa extracellular matrix protein with a cell-binding domain. It is involved cell adhesion and cell migration and is therefore considered to influence tumorigenesis and/or metastasis. The purpose of the present study was to evaluate the clinical significance of Osteopontin expression in oesophageal squamous cell carcinoma (ESCC). In the present study, we immunohistochemically investigated the relationship between Osteopontin expression and clinicopathological factors including prognosis in surgical specimens of primary tumours in 175 patients with ESCC. Osteopontin was expressed in 48% of 175 patients. Osteopontin expression was significantly correlated with lymph node metastasis, lymphatic invasion, and stage (P ¼ 0.0015, 0.037 and 0.033, respectively). Tumours with expressing Osteopontin exhibited more lymph node metastasis, lymphatic invasion and advanced stage than the tumour with negative Osteopontin expression. Five-year survival rate was better in patients with negative Osteopontin expression than in those with positive Osteopontin expression (P ¼ 0.035). However, multivariate analysis revealed that Osteopontin expression was not an independent prognostic factor. As our findings suggest that Osteopontin may play an important role in progress of ESCC, the evaluation of Osteopontin expression is useful for predicting the malignant properties of ESCC.

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Section: Discussionmentioning

confidence: 99%

Expression of Osteopontin in oesophageal squamous cell carcinoma

et al. 2006

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“…Indeed, the Tyr 261 and the Asp 172 correspond to a heparin binding site and a phosphorylation site overlapped by the homologous Itga 4 b 1 binding site of fibronectin, respectively [15]. Asn 126 neighbors the RGDS motif that serves as a binding site for Itga v b 1 [36], a v b 3 [37], and a v b 5 [38]. The critical substitutions for the functional differences of allelic OPNs need to be identified.…”

Section: Discussionmentioning

confidence: 99%

Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice

Miyazaki

Ono

et al. 2005

Eur J Immunol

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Potentially, autoimmune diseases develop from a combination of multiple genes with allelic polymorphisms. An MRL/Mp-Fas lpr/lpr (MRL/lpr) strain of mice develops autoimmune diseases, including lupus nephritis, but another lpr strain, C3H/HeJFas lpr/lpr (C3H/lpr) does not. This indicates that MRL polymorphic genes are involved in the development of the diseases. By quantitative trait loci (QTL) analysis using 527 of the (MRL/lpr Â C3H/lpr)F 2 mice, we identified a novel locus for susceptibility to lupus nephritis at map position D5Mit115 on chromosome 5, the same alias of the osteopontin (Opn) gene (LOD score =4.0), susceptible in the MRL allele. In functional analyses of the MRL and C3H Opn alleles using synthetic osteopontin (OPN) made with a new method "cell-free system" with wheat germ ribosomes, the MRL-OPN induced higher expression and production of immunoglobulins as well as cytokines including TNF-a, IL-1b and IFN-c in splenocytes and/or macrophages than that of the C3H allele. These findings suggest that allelic polymorphism of OPN causes the functional differences in antibody production and macrophage activation between MRL and C3H strains, possibly involved in the development of lupus nephritis.

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“…Using the same procedure, the effect of the compound on ␣ v ␤ 1 function was determined through inhibition of binding of the human embryonic kidney cell line 293, which constitutively expresses this integrin (27), to purified human vitronectin (5.0 g/ml). An ␣ v ␤ 5 -specific functional assay similar to that characterized by Hu et al (28) was developed through stable transfection of the 293 cells with cDNA encoding the human integrin ␤ 5 subunit, and performed as above, in plates coated with 0.3 g/ml vitronectin. Integrin specificity was confirmed in all cell-based adhesion assays with appropriate control antibodies.…”

Section: Methodsmentioning

confidence: 99%