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
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.
Available from: Yong Poovorawan
- "Thus, the identification of alternative serum markers of HBV-related HCC is needed, particularly in low-resource regions with high incidence of HCC. O s t e o p o n t i n ( O P N ) , a n i n t e g r i n -b i n d i n g glycophosphoprotein, is expressed by several cell types and has been involved in both normal and pathological processes, such as cell adhesion, chemotaxis, matrix degradation, angiogenesis and apoptosis (Denhardt et al., 2001; Furger et al., 2001). It has been shown that OPN is over-expressed and associated with tumor invasion, progression and metastasis in various cancers, including HCC (Khodavirdi et al., 2006; Rohde et al., 2007; Korita et al., 2008; Sieghart et al., 2011). "
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ABSTRACT: Background: The aims of this study were to evaluate the diagnostic and prognostic roles of serum osteopontin (OPN) and single nucleotide polymorphisms (SNPs) in the OPN promoter in patients with hepatitis B-related hepatocellular carcinoma (HCC). Materials and Methods: Four groups were studied, which included 157 patients with HCC, 73 with liver cirrhosis (LC) and 97 with chronic hepatitis (CH), along with 80 healthy subjects. Serum OPN and alpha-fetoprotein (AFP) levels were measured. The SNPs -66 T/G, -156 G/ΔG and -433 C/T within the OPN promoter were determined by direct sequencing. Results: Serum OPN levels were significantly higher in patients with HCC than in the other groups. Area under receiver operating characteristics curves in distinguishing HCC from chronic liver disease (CLD; CH and LC) were 0.782 (95% CI; 0.729-0.834) for OPN and 0.888 (95% CI; 0.850-0.927) for AFP. Using the optimal cut-offvalue (70 ng/mL), OPN had sensitivity and specificity of 72% and 71%, respectively. Serum OPN was superior to AFP in detecting early-stage HCC (68% vs. 46%). A combination of both markers yielded an improved sensitivity for detecting early HCC to 82%. A high OPN level was significantly correlated with advanced BCLC stage and was an independent prognostic factor for HCC. The SNPs -156 and -443 were associated with susceptibility to HCC, but were not related to overall survival. Conclusions: Serum OPN is a useful diagnostic and prognostic marker for HCC. The combined use of serum OPN and AFP improved the diagnosis of early HCC. Genetic variation in the OPN promoter is associated with the risk, but not the prognosis of HCC.
Available from: Romina Sepe
- "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 –. 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 –. 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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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.
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.
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.
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.
Available from: Judith-Anne W Chapman
- "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.
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