The Functional and Clinical Roles of Osteopontin in Cancer and Metastasis

London Regional Cancer Centre, Ontario, Canada.
Current Molecular Medicine (Impact Factor: 3.61). 12/2001; 1(5):621-32. DOI: 10.2174/1566524013363339
Source: PubMed

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.

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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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    • "Among them, SPARC (secreted protein acidic rich in cysteine), thrombospondins , and osteopontin (OPN) have been reported to play a pivotal role in providing proliferative and antiapoptotic signals to cancer cells, influencing their binding to structural matrix components or directly triggering tumour cell surface receptors [70]. Through the engagement of specific integrin receptors or CD44, OPN exerts its pleiotropic function in cancer cell survival, ECM remodelling, cell migration, and metastasis in solid cancers as well as in aggressive B-cell lymphomas [71] [72] [73] [74] [75]. One of the mechanisms hypothesized as responsible for the promotion of neoplastic cell survival by OPN relies on its binding to CD44. "
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    ABSTRACT: Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.
    Advances in Hematology 02/2012; 2012:138079. DOI:10.1155/2012/138079
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    • "Osteopontin (OPN) is a secreted transformation-associated phosphoprotein and has been implicated in tumorigenesis . The upregulation of OPN expression has also been reported in a variety of human cancers, such as breast, prostate, nonsmall cell lung cancer (NSCLC), and colon carcinomas [14]. Importantly, several studies have suggested a relationship between OPN levels and the progression of these cancers [15] [16] [17] [18]. "
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    ABSTRACT: The multistep process of metastasis is a major hallmark of cancer progression involving the cointeraction and coevolution of the tumor and its microenvironment. In the tumor microenvironment, tumor cells and the surrounding stromal cells aberrantly secrete matricellular proteins, which are a family of nonstructural proteins in the extracellular matrix (ECM) that exert regulatory roles via a variety of molecular mechanisms. Matricellular proteins provide signals that support tumorigenic activities characteristic of the metastastic cascade such as epithelial-to-mesenchymal (EMT) transition, angiogenesis, tumor cell motility, proliferation, invasion, evasion from immune surveillance, and survival of anoikis. Herein, we review the current understanding of the following matricellular proteins and highlight their pivotal and multifacted roles in metastatic progression: angiopoietin-like protein 4 (ANGPTL4), CCN family members cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) and CCN6, osteopontin (OPN), secreted protein acidic and rich in cysteine (SPARC), tenascin C (TNC), and thrombospondin-1 and -2 (TSP1, TSP2). Insights into the signaling mechanisms resulting from the interaction of these matricellular proteins and their respective molecular partner(s), as well as their subsequent contribution to tumor metastasis, are discussed. In addition, emerging evidences of their promising potential as therapeutic options and/or targets in the treatment of cancer are also highlighted.
    Journal of Oncology 02/2012; 2012(3):351089. DOI:10.1155/2012/351089