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Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the past 2 decades. Dickkopf-3 protein (Dkk-3\/REIC) has been known to inhibit canonical Wnt\/<jats:italic>\u03b2<\/jats:italic>-catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Using<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>studies, we demonstrated that Dkk-3-transfected 143B cells inhibited tumorigenesis and metastasis in an orthotopic xenograft model of OS. Inoculation of Dkk-3-transfected 143B cell lines into nude mice showed significant decreased tumor growth and less metastatic pulmonary nodules (88.7%) compared to the control vector.<jats:italic>In vitro<\/jats:italic>experiments examining cellular motility and viability demonstrated less anchorage-independent growth and decreased cellular motility for Dkk-3-transfected 143B and SaOS2 cell lines compared to the control vector. Downstream expressions of Met, MAPK, ALK, and S1004A were also downregulated in Dkk-3-transfected SaOS2 cells, suggesting the ability of Dkk-3 to inhibit tumorigenic potential of OS. Together, these data suggest that Dkk-3 has a negative impact on the progression of osteosarcoma. Reexpressing Dkk-3 in Dkk-3-deficient OS tumors may prove to be of benefit as a preventive or therapeutic strategy.<\/jats:p>","DOI":"10.1155\/2013\/147541","type":"journal-article","created":{"date-parts":[[2013,2,10]],"date-time":"2013-02-10T21:00:48Z","timestamp":1360530048000},"page":"1-11","source":"Crossref","is-referenced-by-count":35,"title":["Dkk-3, a Secreted Wnt Antagonist, Suppresses Tumorigenic Potential and Pulmonary Metastasis in Osteosarcoma"],"prefix":"10.1155","volume":"2013","author":[{"given":"Carol H.","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Oncology, CHOC Children\u2019s Hospital, 455 South Main Street, Orange, CA 92868, USA"},{"name":"Department of Orthopaedic Surgery, University of California, Irvine, 101 The City Drive South, Orange, CA 92868, USA"}]},{"given":"Yi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of California, Irvine, 101 The City Drive South, Orange, 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101 The City Drive South, Orange, CA 92868, USA"}]},{"given":"Tao","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of California, Irvine, 101 The City Drive South, Orange, CA 92868, USA"}]},{"given":"Ramez","family":"Eskander","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of California, Irvine, 101 The City Drive South, Building 56, Suite 260, Orange, CA 92868, USA"}]},{"given":"Xiaolin","family":"Zi","sequence":"additional","affiliation":[{"name":"Department of Urology, University of California, Irvine, 101 The City Drive South, Building 55, Suite 302, Orange, CA 92868, USA"},{"name":"Department of Pharmaceutical Sciences, University of California, Irvine, 101 The City Drive South, Orange, CA 92868, USA"}]},{"given":"Bang H.","family":"Hoang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of California, Irvine, 101 The City 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