The Functional and Clinical Roles of Osteopontin in Cancer and Metastasis

London Regional Cancer Centre, Ontario, Canada.
Current Molecular Medicine (Impact Factor: 3.62). 12/2001; 1(5):621-32. DOI: 10.2174/1566524013363339
Source: PubMed


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.

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    • "In fact, FOS, FOSB and EGR1 are proteins that have been reported to be down-regulated in several human carcinomas suggesting a critical role of these proteins in cancer progression [17]–[19]. On the other hand, SPP1, SPINK1 and STEAP1 are proteins that are up-regulated in several human carcinomas and their overexpression is also associated to cancer progression [20]–[22]. We evaluated the expression of these transcripts by qRT-PCR in several CBX7-expressing FRO clones (Figure 1B and C) compared with FRO-EV clones and with the FRO (wt) cells. "
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    ABSTRACT: Background 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. Methods We analyzed the gene expression profile of a thyroid carcinoma cell line after the restoration of CBX7 and, then, analyzed the transcriptional regulation of identified genes. Finally, we evaluated the expression of CBX7 and regulated genes in a panel of thyroid and lung carcinomas. Results We found that CBX7 negatively or positively regulates the expression of several genes (such as SPP1, SPINK1, STEAP1, and FOS, FOSB, EGR1, respectively) associated to cancer progression, by interacting with their promoter regions and modulating their transcriptional activity. Quantitative RT-PCR analyses in human thyroid and lung carcinoma tissues revealed a negative correlation between CBX7 and its down-regulated genes, while a positive correlation was observed with up-regulated genes. Conclusion In conclusion, the loss of CBX7 expression might play a critical role in advanced stages of carcinogenesis by deregulating the expression of specific effector genes.
    PLoS ONE 05/2014; 9(5):e98295. DOI:10.1371/journal.pone.0098295 · 3.23 Impact Factor
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    • "Thus, elevated OPN levels in both tumor tissue and blood are well-documented to be associated with poor outcome in the setting of metastatic breast cancer [1-5]. However, much less is known about the prognostic significance of OPN in early breast cancer or when OPN levels rise during breast cancer progression. "
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    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. DOI:10.1186/bcr3600 · 5.49 Impact Factor
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    • "Osteopontin (OPN) is a secreted and calcium binding phosphorylated glycoprotein and expressed constitutively in a limited number of normal tissues, stress-responsive physiological conditions, and abnormally elevated in some pathological conditions [10]. OPN is considered as cytokine that regulates cell pathways in the immune system [10] [11]. OPN was also expressed in various malignancies and may play important role in tumorigenesis, tumour invasion, and metastasis in various malignancies [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22]. "
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    ABSTRACT: Background: Osteopontin (OPN) is expressed in various malignancies and may play an important role in tumorigenesis, tumour invasion, and metastasis in various malignancies including thyroid cancers. The objective of this study was to investigate the relationship between OPN immunoexpression and clinicopathological characteristics in thyroid lesions. Material and methods: Paraffin blocks belonging to 160 patients with thyroid neoplasms were retrieved from the archive of the Department of Pathology at King Abdulaziz University, and King Faisal Specialist Hospital, Jeddah, Saudi Arabia. Immunohistochemistry was performed using anti-OPN antibody. Statistical tests were used to determine the relation of OPN immunoexpression to clinicopathological characteristics and survival. Results: Immunostaining results showed that OPN was localised in the cytoplasm and nucleus with higher cytoplasmic expression. Cytoplasmic and nuclear OPN was higher in thyroid cancer than other lesions. Microcarcinoma variant of papillary thyroid carcinoma showed a lower OPN cytoplasmic level than other variants. OPN cytoplasmic expression was not associated with most of the clinicopathological parameters tests. However, OPN cytoplasmic overexpression was associated poor survival outcome (p < 0.001). Conclusion: Upregulation of cytoplasmic OPN was associated with poor survival outcome and was an independent predictor of margin involvement and recurrence. Nuclear OPN expression was lower than cytoplasmic and was associated with extrathyroid extension of thyroid cancer. OPN plays a role in thyroid carcinoma and incoming research has to be focused on the mechanistic association with invasion and metastasis.
    09/2013; 1(1-2):8-16. DOI:10.1016/j.jmau.2013.07.001
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