Plasma Osteopontin Is an Independent Prognostic Marker for Head and Neck Cancers

Petrik, David; Lavori, Philip W.; Cao, Hongbin; Zhu, Y.; Wong, Priscilla H.; Christofferson, Erin; Kaplan, Michael; Pinto, Harlan A.; Sutphin, Patrick D.; Koong, Albert C.; Giaccia, Amato J.; Le, Quynh‐Thu

doi:10.1200/jco.2006.06.8627

Cited by 57 publications

(42 citation statements)

References 27 publications

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“…These findings were supported by an in vivo study which found that intratumoral and plasma OPN levels were dependent on the strains of mice and tumour models, and OPN levels were increased by reoxygenation rather than prolonged hypoxia exposure (32). Despite the uncertainty of OPN as a true hypoxic biomarker, plasma OPN has been shown to be a significant prognostic marker in HNSCC (28,33). Although immunohistochemistry is easy to perform in clinical practice, these endogenous markers are not purely specific to hypoxia and may be affected by other biological processes in the tumour microenvironment (34).…”

Section: Evidence Of Hypoxia In Npcsupporting

confidence: 63%

Clinical significance of hypoxia in nasopharyngeal carcinoma with a focus on existing and novel hypoxia molecular imaging

Yip¹,

Cook

Wee

et al. 2016

Chin. Clin. Oncol.

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Section: Evidence Of Hypoxia In Npcsupporting

confidence: 63%

Clinical significance of hypoxia in nasopharyngeal carcinoma with a focus on existing and novel hypoxia molecular imaging

Yip¹,

Cook

Wee

et al. 2016

Chin. Clin. Oncol.

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“…Furthermore, they were able to show that a high level of plasma osteopontin correlated with tumor hypoxia (pO2 as measured by Eppendorf electrode) and was associated with poor clinical outcome in head and neck cancer patients (11). An expanded follow-up study has further confirmed high plasma osteopontin as an independent predictor for tumor control and overall survival (12).…”

mentioning

confidence: 61%

Plasma Osteopontin, Hypoxia, and Response to Radiotherapy in Nasopharyngeal Cancer

Hui

Sung

et al. 2008

Clinical Cancer Research

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Purpose: Recent studies have suggested that osteopontin is induced by hypoxia in head and neck cancer cell lines and its plasma level may serve as a surrogate marker for tumor hypoxia and treatment outcome in head and neck cancer.We investigated the response of osteopontin to in vitro hypoxia in nasopharyngeal carcinoma cell lines, and determined plasma osteopontin levels in nasopharyngeal carcinoma patients, nonnasopharyngeal carcinoma head and neck cancer patients, and healthy controls.We explored the relationship of plasma osteopontin and response to radiotherapy in nasopharyngeal carcinoma. Experimental Design: Nasopharyngeal carcinoma cell lines HK1, HONE-1, C666-1, and CNE-2 were treated with 0 to 48 hours of hypoxia or normoxia, +/-reoxygenation. Osteopontin secretion in the supernatant was measured by ELISA assay. Cellular osteopontin protein and mRNA were detected by Western blotting and reverse transcription-PCR, respectively. Plasma osteopontin levels in patients (n = 66; 44 nasopharyngeal carcinoma, 22 head and neck cancer) and controls (n = 29) were measured by ELISA. Results: Hypoxia has no effect on osteopontin protein and mRNA level in nasopharyngeal carcinoma cells. Only CNE-2 secreted osteopontin, and there was no significant induction by hypoxia. Plasma osteopontin levels in patients of metastatic nasopharyngeal carcinoma and head and neck cancer, but not in locoregional nasopharyngeal carcinoma, were significantly higher than in controls. In patients with locoregional nasopharyngeal carcinoma receiving curative radiotherapy (n = 31), a high (>median) pretreatment plasma osteopontin level was a significant predictor of poor response to radiotherapy (complete response rate, 40 % versus 88 %; P = 0.009), which remained significant in multivariate analysis. Conclusion: Our results suggested that the pretreatment plasma osteopontin level may be a useful biomarker of response to radiotherapy in nasopharyngeal carcinoma.

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“…Transglutamination of OPN can facilitate covalent binding to fibronectin, creating a strong adhesive link between these proteins in the ECM (26). While the earliest studies of OPN suggested that it had a central role in bone remodeling and cancer metastasis (27)(28)(29)(30), subsequent studies demonstrated that OPN also participates in numerous other physiological processes such as formation of collagen fibrils during tissue remodeling (31), macrophage and neutrophil migration (32,33), angiogenesis (28), and wound healing (31). OPN binding to integrins on the surface of immune cells is likely the mechanism by which OPN modulates chemotaxis of these cells.…”

Section: Introductionmentioning

confidence: 99%

Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-β

Vetrone¹,

Montecino‐Rodriguez²,

Kudryashova³

et al. 2009

J. Clin. Invest.

260

309

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Duchenne muscular dystrophy (DMD) is an X-linked, degenerative muscle disease that is exacerbated by secondary inflammation. Here, we characterized the immunological milieu of dystrophic muscle in mdx mice, a model of DMD, to identify potential therapeutic targets. We identified a specific subpopulation of cells expressing the Vβ8.1/8.2 TCR that is predominant among TCR-β + T cells. These cells expressed high levels of osteopontin (OPN), a cytokine that promotes immune cell migration and survival. Elevated OPN levels correlated with the dystrophic process, since OPN was substantially elevated in the serum of mdx mice and muscle biopsies after disease onset. Muscle biopsies from individuals with DMD also had elevated OPN levels. To test the role of OPN in mdx muscle, mice lacking both OPN and dystrophin were generated and termed doublemutant mice (DMM mice). Reduced infiltration of NKT-like cells and neutrophils was observed in the muscle of DMM mice, supporting an immunomodulatory role for OPN in mdx muscle. Concomitantly, an increase in CD4 + and FoxP3 + Tregs was also observed in DMM muscle, which also showed reduced levels of TGF-β, a known fibrosis mediator. These inflammatory changes correlated with increased strength and reduced diaphragm and cardiac fibrosis. These studies suggest that OPN may be a promising therapeutic target for reducing inflammation and fibrosis in individuals with DMD.

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Plasma Osteopontin Is an Independent Prognostic Marker for Head and Neck Cancers

Abstract: In this expanded study, we were able to replicate the prognostic significance of OPN using a predefined cut off point in an independent patient group and demonstrated that plasma OPN is an independent prognostic marker for HNSCC.

Cited by 57 publications

References 27 publications

Clinical significance of hypoxia in nasopharyngeal carcinoma with a focus on existing and novel hypoxia molecular imaging

Clinical significance of hypoxia in nasopharyngeal carcinoma with a focus on existing and novel hypoxia molecular imaging

Plasma Osteopontin, Hypoxia, and Response to Radiotherapy in Nasopharyngeal Cancer

Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-β

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