Wnt inhibitory factor 1 decreases tumorigenesis and metastasis in osteosarcoma

Elyssa M. Rubin, Yi Guo, Khoa Tu, Jun Xie, Xiaolin Zi, Bang H. Hoang

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

It has been reported that the progression of osteosarcoma was closely associated with the aberrant activation of canonical Wnt signaling. Wnt inhibitory factor-1 (WIF-1) is a secreted Wnt inhibitor whose role in human osteosarcoma remains unknown. In this study, WIF-1 expression in NHOst and osteosarcoma cell lines was determined by real-time reverse transcription-PCR, methylation-specific PCR, and Western blotting analysis. In addition, tissue array from patient samples was examined for WIF-1 expression by immunohistochemistry. Compared with normal human osteoblasts, WIF-1 mRNA and protein levels were significantly downregulated in several osteosarcoma cell lines. The downregulation of WIF-1 mRNA expression is associated with its promoter hypermethylation in these tested cell lines. Importantly, WIF-1 expression was also downregulated in 76% of examined osteosarcoma cases. These results suggest that the downregulation of WIF-1 expression plays a role in osteosarcoma progression. To further study the potential tumor suppressor function of WIF-1 in osteosarcoma, we established stable 143B cell lines overexpressing WIF-1. WIF-1 over-expression significantly decreased tumor growth rate in nude mice as examined by the s.c. injection of 143B cells stably transfected with WIF-1 and vector control. WIF-1 overexpression also markedly reduced the number of lung metastasis in vivo in an orthotopic mouse model of osteosarcoma. Together, these data suggest that WIF-1 exerts potent antiosteosarcoma effect in vivo in mouse models. Therefore, the reexpression of WIF-1 in WIF-1-deficient osteosarcoma represents a potential novel treatment and preventive strategy.

Original languageEnglish (US)
Pages (from-to)731-741
Number of pages11
JournalMolecular Cancer Therapeutics
Volume9
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

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Wnt Proteins
Osteosarcoma
Carcinogenesis
Neoplasm Metastasis
Down-Regulation
Cell Line
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wnt inhibitory factor 1 decreases tumorigenesis and metastasis in osteosarcoma. / Rubin, Elyssa M.; Guo, Yi; Tu, Khoa; Xie, Jun; Zi, Xiaolin; Hoang, Bang H.

In: Molecular Cancer Therapeutics, Vol. 9, No. 3, 03.2010, p. 731-741.

Research output: Contribution to journalArticle

Rubin, Elyssa M. ; Guo, Yi ; Tu, Khoa ; Xie, Jun ; Zi, Xiaolin ; Hoang, Bang H. / Wnt inhibitory factor 1 decreases tumorigenesis and metastasis in osteosarcoma. In: Molecular Cancer Therapeutics. 2010 ; Vol. 9, No. 3. pp. 731-741.
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