Dkk-3, a secreted wnt antagonist, suppresses tumorigenic potential and pulmonary metastasis in osteosarcoma

Carol H. Lin, Yi Guo, Samia Ghaffar, Peter McQueen, Jonathan Pourmorady, Alexander Christ, Kevin Rooney, Tao Ji, Ramez Eskander, Xiaolin Zi, Bang H. Hoang

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. 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/β-catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Using in vivo and in vitro 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. In vitro 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.

Original languageEnglish (US)
Article number147541
JournalSarcoma
Volume2013
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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    Lin, C. H., Guo, Y., Ghaffar, S., McQueen, P., Pourmorady, J., Christ, A., Rooney, K., Ji, T., Eskander, R., Zi, X., & Hoang, B. H. (2013). Dkk-3, a secreted wnt antagonist, suppresses tumorigenic potential and pulmonary metastasis in osteosarcoma. Sarcoma, 2013, [147541]. https://doi.org/10.1155/2013/147541