NON-THEMATIC REVIEW

Cancer and Metastasis Reviews

, Volume 27, Issue 1, pp 103-118

Osteopontin: regulation in tumor metastasis

  • Philip Y. WaiAffiliated withDepartment of Surgery, Duke University Medical Center
  • , Paul C. KuoAffiliated withDepartment of Surgery, Duke University Medical Center Email author 

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Abstract

Osteopontin is a secreted phosphoprotein that has been implicated as an important mediator of tumor metastasis and has been investigated for use as a biomarker for advanced disease and as a potential therapeutic target in the regulation of cancer metastasis. The OPN DNA sequence is highly conserved and the protein contains several important functional domains including αvβ integrin and CD44 binding sites. High levels of OPN expression correlate with tumor invasion, progression or metastasis in multiple cancer. Studies demonstrate that osteopontin mediates the molecular mechanisms which determine metastatic spread, such as prevention of apoptosis, extracellular matrix proteolysis and remodeling, cell migration, evasion of host-immune cells and neovascularization. Transcriptional regulation of OPN is complex and involves multiple pathways, including AP-1, Myc, v-Src, Runx/CBF, TGF-B/BMPs/Smad/Hox, and Wnt/ß–catenin/APC/GSK–3ß/Tcf-4. The current state of knowledge of OPN biology suggests that it is an attractive target for therapeutic modulation of metastatic disease.

Keywords

Cancer Metastasis Osteopontin Integrin Matrix-metalloproteinase