The functional and clinical roles of osteopontin in cancer and metastasis.
ABSTRACT Osteopontin (OPN) is a secreted and integrin-binding protein that has been implicated in a number of pathologies. In this review we will focus on the functional and clinical roles of OPN in cancer and metastasis, with a particular emphasis on breast cancer. While much evidence has suggested that OPN is associated with cancer, its functional contribution to cancer remains poorly understood. Here we will review evidence for mechanisms by which OPN may act to enhance malignancy, including evidence that signaling pathways directly induced by OPN, as well as interactions with growth factor receptor pathways, can combine to activate expression of genes and functions that contribute to metastasis. OPN has been shown to be over-expressed in a variety of human tumors and is present in elevated levels in the blood of some patients with metastatic cancers. We also will discuss recent clinical evidence that suggests that OPN is not only associated with several tumor types, but that levels of OPN in cancer patients' blood or tumors may provide prognostic information.
- SourceAvailable from: Judith-Anne W Chapman[Show abstract] [Hide abstract]
ABSTRACT: Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis. We measured OPN in plasma by ELISA, and in tumor by immunohistochemistry, in 624 (94%) and 462 (69%) respectively of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/- octreotide in a randomized trial (NCIC CTG MA.14). Plasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 - 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI 30.2 - 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 - 543) in the recurrence period compared with baseline levels. The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study.Trial registration: NCT00002864.Breast cancer research: BCR 01/2014; 16(1):R8. · 5.87 Impact Factor
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ABSTRACT: Osteopontin (OPN) plays a role in tumor progression. This study aimed to determine the expression of OPN, CD44, and integrin αvβ3 in pleomorphic adenoma (PA), polymorphous low-grade adenocarcinoma (PLGA), and adenoid cystic carcinoma (ACC). Immunohistochemistry was used to semiquantify the level of expression of OPN and its receptors in normal salivary glands (NSG; n = 20), PA (n = 20), PLGA (n = 16), and ACC (n = 22). OPN expression was increased in PLGA and intermediate-/high-grade ACC compared with PA and NSG (median scores, 6, 5, 4, and 4, respectively). CD44 expression was reduced in PA, PLGA, and ACC. OPN expression levels were moderately correlated with CD44 in PLGA. Integrin αvβ3 was not expressed in PA and ACC and was seen in only 1 case of PLGA. OPN is expressed in salivary gland tumors but does not correlate well with CD44 and αvβ3.Oral surgery, oral medicine, oral pathology and oral radiology. 12/2013; 116(6):743-51.
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ABSTRACT: We have previously shown that the expression of CBX7 is drastically decreased in several human carcinomas and that its expression progressively decreases with the appearance of a highly malignant phenotype. The aim of our study has been to investigate the mechanism by which the loss of CBX7 expression may contribute to the emergence of a more malignant phenotype.PLoS ONE 01/2014; 9(5):e98295. · 3.73 Impact Factor