Osteopontin increases lung cancer cells migration via activation of the αvβ3 integrin/FAK/Akt and NF-κB-dependent pathway

Fong, Yi‐Chin; Liu, Shan‐Chi; Huang, Chun‐Yin; Li, Te‐Mao; Hsu, Sheng-Feng; Kao, Shung‐Te; Tsai, Fuu‐Jen; Chen, Wen‐Chi; Chen, Chih-Yi; Tang, Chih‐Hsin

doi:10.1016/j.lungcan.2008.09.003

Cited by 113 publications

(88 citation statements)

References 37 publications

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“…There were some preliminary indications, in previous studies and in our own experiments, suggesting that several signaling pathways are involved in other properties of OPN, e.g., T cell survival (25,26) and tumor metastasis (27)(28)(29). However, the details regarding how OPN regulates the expression of proinflammatory chemokines, such as MCP-1 and MIP-1␤, remain unclear.…”

Section: Resultsmentioning

confidence: 76%

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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Section: Resultsmentioning

confidence: 76%

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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“…In tumor cells, cellular processes, including proliferation, migration, and invasion, are known to be regulated, at least in part, by ERKs and AKT signaling pathways that have been shown to be activated by OPN (11,41,59). The present study demonstrates that pulmonary vascular remodeling in chronic hypoxic PH is associated with emergence of adventitial fibroblasts (PH-Fibs) with constitutively activated ERK1/2 and AKT signaling that is dependent on OPN expression levels.…”

Section: Discussionmentioning

confidence: 99%

“…Since PH-Fibs exhibited high proliferative, migratory, and proinvasive capabilities under serum-free conditions, and this phenotype was maintained over numerous passages in culture (i.e., exhibited a "constitutively" activated phenotype), we next investigated the status of ERK1/2 and AKT signaling pathways that are known to contribute, at least in part, to cell proliferation, migration, and invasion (11,41,59). Under basal, serumfree conditions, PH-Fibs had markedly elevated levels of phospho-AKT and phospho-ERK1/2 compared with CO-Fibs (Fig.…”

Section: Opn Contributes To Constitutively Activated Erk and Akt Signmentioning

confidence: 99%

Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension

Anwar

Frid

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 303: L1-L11, 2012. First published May 11, 2012; doi:10.1152/ajplung.00050.2012.-Increased cell proliferation and migration, of several cell types are key components of vascular remodeling observed in pulmonary hypertension (PH). Our previous data demonstrate that adventitial fibroblasts isolated from pulmonary arteries of chronically hypoxic hypertensive calves (termed PH-Fibs) exhibit a "constitutively activated" phenotype characterized by high proliferative and migratory potential. Osteopontin (OPN) has been shown to promote several cellular activities including growth and migration in cancer cells. We thus tested the hypothesis that elevated OPN expression confers the "activated" highly proproliferative and promigratory/invasive phenotype of PH-Fibs. Our results demonstrate that, both in vivo and ex vivo, PH-Fibs exhibited increased expression of OPN, as well as its cognate receptors, ␣ V␤3 and CD44, compared with control fibroblasts (CO-Fibs). Augmented OPN expression in PH-Fibs corresponded to their high proliferative, migratory, and invasive properties and constitutive activation of ERK1/2 and AKT signaling. OPN silencing via small interfering RNA or sequestering OPN production by specific antibodies led to decreased proliferation, migration, invasion, and attenuated ERK1/2, AKT phosphorylation in PH-Fibs. Furthermore, increasing OPN levels in CO-Fibs via recombinant OPN resulted in significant increases in their proliferative, migratory, and invasive capabilities to the levels resembling those of PH-Fibs. Thus our data suggest OPN as an essential contributor to the activated (highly proliferative, migratory, and proinvasive) phenotype of pulmonary adventitial fibroblasts in hypoxic PH. vascular remodeling; inflammation; matricellular protein; extracellular matrix protein; vascular proliferation ALL FORMS OF CHRONIC PULMONARY hypertension (PH) are characterized by structural and fibroproliferative changes in both small and large pulmonary arteries (PAs) through a process termed vascular remodeling. Remodeling can affect all layers of the vessel wall and involves changes in the phenotype and functional behavior of each of the principal cell types in the vessel wall. However, one of the most consistent findings in experimental models of PH, as well as in models of vascular injury and hypertension in the systemic circulation, is early and dramatic adventitial remodeling, characterized by fibroblast proliferation, migration, and differentiation (5, 33, 53-55, 58, 64, 65). Although the mechanisms involved in these responses remain obscure, the possibility that they are coordinated through interactions with surrounding extracellular matrix (ECM) proteins is one possible mechanism (55, 58).

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“…Thus, OPN functions between tumor cells and mesenchyme mainly through such exterior molecules. On the other hand, binding of OPN may also activate several inner downstream signaling pathways, such as phosphatidylinositol 3-kinase/protein kinase B, nuclear factor-κB and urokinase plasminogen, which were also proven to be involved in tumors (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Osteopontin is overexpressed in colorectal carcinoma and is correlated with P53 by immunohistochemistry

Li¹,

Yang²,

Zhu

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Osteopontin (OPN), a secreted phosphorylated glycoprotein, has been found to be involved in carcinogenesis, progression and metastasis of several types of cancers. The aim of the present study was to investigate the immunohistochemical expression of OPN in colorectal carcinoma (CRC) and its relationship with clinicopathological parameters and P53. Expression of OPN, Ki-67 and TP53 was detected in 77 cases of CRC by immunohistochemistry and the correlation of the expression of OPN with clinicopathological features, Ki-67 and P53 staining was investigated. Thirty-eight cases (49.4%) of CRC demonstrated OPN overexpression. Overexpression of OPN was associated with lymph node metastasis (P=0.025) and Dukes' stages (P=0.031), but not with gender, histological differentiation, depth of tumor invasion, TNM stages or Ki-67 index. The correlation between expression of OPN and TP53 was statistically significant (P=0.030). In conclusion, OPN is overexpressed in CRC, and plays a role in tumor progression and metastasis, which is possibly regulated by P53.

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Osteopontin increases lung cancer cells migration via activation of the αvβ3 integrin/FAK/Akt and NF-κB-dependent pathway

Cited by 113 publications

References 37 publications

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

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

Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension

Osteopontin is overexpressed in colorectal carcinoma and is correlated with P53 by immunohistochemistry

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