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The Role of Osteopontin in Tumor Progression and Metastasis in Breast Cancer

¹ Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Campus de Gualtar, Braga, Portugal; ² Instituto de Patologia e Imunologia Molecular, ³ Faculdade de Medicina, Universidade do Porto, Oporto, Portugal; ⁴ Department of Food Technology, Engineering, and Nutrition, Lund University; and ⁵ Swedish Dairy Association, Lund, Sweden

Requests for reprints: Lígia Rodrigues, Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Campus de Gualtar, 4710-057 Braga, Portugal. Phone: 351-2536-04400; Fax: 351-2536-78986. E-mail: lrmr{at}deb.uminho.pt.

The use of cancer biomarkers to anticipate the outlines of disease has been an emerging issue, especially as cancer treatment has made such positive steps in the last few years. Progress in the development of consistent malignancy markers is imminent because advances in genomics and bioinformatics have allowed the examination of immense amounts of data. Osteopontin is a phosphorylated glycoprotein secreted by activated macrophages, leukocytes, and activated T lymphocytes, and is present in extracellular fluids, at sites of inflammation, and in the extracellular matrix of mineralized tissues. Several physiologic roles have been attributed to osteopontin, i.e., in inflammation and immune function, in mineralized tissues, in vascular tissue, and in kidney. Osteopontin interacts with a variety of cell surface receptors, including several integrins and CD44. Binding of osteopontin to these cell surface receptors stimulates cell adhesion, migration, and specific signaling functions. Overexpression of osteopontin has been found in a variety of cancers, including breast cancer, lung cancer, colorectal cancer, stomach cancer, ovarian cancer, and melanoma. Moreover, osteopontin is present in elevated levels in the blood and plasma of some patients with metastatic cancers. Therefore, suppression of the action of osteopontin may confer significant therapeutic activity, and several strategies for bringing about this suppression have been identified. This review looks at the recent advances in understanding the possible mechanisms by which osteopontin may contribute functionally to malignancy, particularly in breast cancer. Furthermore, the measurement of osteopontin in the blood or tumors of patients with cancer, as a way of providing valuable prognostic information, will be discussed based on emerging clinical data. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1087–97)