Dkk-3, a Secreted Wnt Antagonist, Suppresses Tumorigenic Potential and Pulmonary Metastasis in Osteosarcoma
| Autor: | Alexander B. Christ, Kevin Rooney, Jonathan Pourmorady, Carol H. Lin, Peter McQueen, Tao Ji, Ramez N. Eskander, Samia Ghaffar, Bang H. Hoang, Yi Guo, Xiaolin Zi |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
MAPK/ERK pathway
Pathology medicine.medical_specialty Article Subject medicine.disease_cause lcsh:RC254-282 Metastasis 03 medical and health sciences 0302 clinical medicine In vivo Medicine and Health Sciences Medicine Radiology Nuclear Medicine and imaging 030304 developmental biology 0303 health sciences business.industry Wnt signaling pathway lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease In vitro 3. Good health Oncology Cell culture 030220 oncology & carcinogenesis Cancer research Osteosarcoma business Carcinogenesis Research Article |
| Zdroj: | Lin, Carol H.; Guo, Yi; Ghaffar, Samia; McQueen, Peter; Pourmorady, Jonathan; Christ, Alexander; et al.(2013). Dkk-3, a Secreted Wnt Antagonist, Suppresses Tumorigenic Potential and Pulmonary Metastasis in Osteosarcoma. Sarcoma, 2013. UC Irvine: Institute for Clinical and Translational Science. Retrieved from: http://www.escholarship.org/uc/item/00m6x6xn Sarcoma, Vol 2013 (2013) Sarcoma |
| Popis: | 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. Usingin vivoandin vitrostudies, 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 vitroexperiments 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. |
| Databáze: | OpenAIRE |
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