Osteopontin: Role in immune regulation and stress responses

Wang, Kathryn X.; Denhardt, David T.

doi:10.1016/j.cytogfr.2008.08.001

Cited by 596 publications

(558 citation statements)

References 151 publications

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“…Furthermore, crosslinking of CD44 results in higher expression levels of lymphocyte function-associated antigen-1 (LFA-1) and VLA-4 which are responsible for enhanced transendothelial migration of tumor cells [38]. The cytoplasmic tail cooperates with intracellular molecules as members of the Src tyrosine kinase family including c-Src, Lyn, Fyn, and Lck [42][43][44][45], Moesin-Ezrin-Radixin-Like Protein Merlin [46], T-cell lymphoma invasion and metastasis-inducing protein 1 and 2 (Tiam1/2) [47], intracellular OPN [48], as well as members of the Smad protein family [14,49,50].…”

Section: Ligands and Protein Interactionsmentioning

confidence: 99%

CD44 in hematological neoplasias

2011

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Section: Ligands and Protein Interactionsmentioning

confidence: 99%

CD44 in hematological neoplasias

2011

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“…It has been recognized as an important proinflammatory cytokine with pleiotropic functions, including activities related to Th1 properties, adhesion, and migration (16)(17)(18)(19)(20)(21). OPN has several functional domains, such as the thrombin cleavage site (RSK) and the GRGDS sequence, through which it interacts with a variety of cell surface receptors, including integrins and CD44.…”

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confidence: 99%

Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

Zheng¹,

R²,

Pan³

et al. 2009

Arthritis & Rheumatism

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Objective. Osteopontin (OPN) is a proinflammatory protein with a critical role in leukocyte migration. Although OPN has been implicated in rheumatoid arthritis (RA), its underlying mechanism remains unknown. In this study, we investigated the role and molecular mechanism of OPN in the induction of 2 key chemokines, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1␤ (MIP-1␤), in RA.Methods. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction were used to determine chemokine expression. Leukocyte migration in the presence of OPN was measured by chemotaxis assay. Signaling and molecular events were analyzed by immunoblotting and chromatin immunoprecipitation.Results. The effect of OPN on inflammatory cell migration was mediated through its unique property of inducing the expression of MCP-1 and MIP-1␤ in CD14؉ monocytes. The concentration of OPN was significantly elevated in RA patients and appeared to correlate with the serum levels of inflammation markers and increased expression of MCP-1 or MIP-1␤ in monocytes in RA patients. Endogenous production of OPN in RA synovial fluid was attributable to increased production of MCP-1 or MIP-1␤, and this effect could be blocked by an anti-OPN antibody. Furthermore, the structural motif responsible for this property resided within residues 50-83 of human OPN, sparing the known RGD or SVVYGLR sequences. It was evident that the effect of OPN on chemokine expression was mediated through both the NF-B and MAPK pathways, involving the activation of IKK␤, p38, and JNK.Conclusion. These results support a unique role of OPN in leukocyte migration, in the context of perpetuation of rheumatoid synovitis through the induction of MCP-1 and MIP-1␤.

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“…Osteopontin (OPN) is a multifunctional extracellular matrix protein that is produced by numerous cell types [6][7][8][9][10][11]. OPN plays important roles in cancer cell adhesion, cell motility, and survival [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

The role of osteopontin expression in melanoma progression

et al. 2015

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It was shown that osteopontin (OPN), a glycophosphoprotein, plays divergent roles in cancer progression. In addition to multiple intra-and extracellular functions, it facilitates migration of tumor cells, has crucial role in cell adhesion and is associated with increased metastasis formation. In previous studies, we performed global gene-expression profiling on a series of primary melanoma samples and found that OPN was significantly overexpressed in ulcerated melanomas. The major purpose of this study was to define OPN expression in primary melanomas with differing biological behaviours. OPN mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in primary melanoma tissues. Immunohistochemistry was performed using a tissue microarray. Cox regression tests were used for survival analysis. Greater than 50% of the tissues exhibited high protein expression that was significantly associated with tumor thickness and metastasis. OPN mRNA expression was significantly increased in thicker melanomas and lesions with an ulcerated surface. Increased expression was primarily detected in advanced-stage tumors. A multivariate Cox regression analysis revealed that high OPN expression, tumor thickness, and metastasis were significantly associated with reduced relapse-free survival. In summary, high OPN mRNA and protein expression were associated with a less favourable clinical outcome of primary melanoma patients. We determined that OPN is a significant predictive factor for the survival of primary melanoma patients. Based on our and others data the high expression of OPN may have a crucial stimulatory role in tumor progression and metastasis formation, thus, have been proposed as potential targets for cancer diagnosis and therapy.3

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Osteopontin: Role in immune regulation and stress responses

Cited by 596 publications

References 151 publications

CD44 in hematological neoplasias

CD44 in hematological neoplasias

Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

The role of osteopontin expression in melanoma progression

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