Tumor Biology

, Volume 37, Issue 5, pp 6315–6321 | Cite as

Enhanced Wnt signaling by methylation-mediated loss of SFRP2 promotes osteosarcoma cell invasion

  • Qiang Xiao
  • Yu Yang
  • Xuepu Zhang
  • Qing An
Original Article


Wnt signaling is essential for the initiation and progression of osteosarcoma (OS) tumors and is suppressed by the secreted frizzled-related proteins (SFRPs). The methylation-induced protein degradation reduces the activity of SFRPs and subsequently increases the activity of Wnt signaling. However, whether the methylation of SFRP2, a member of SFRPs, may be involved in the pathogenesis of OS is not known. Here, we investigated the expression levels of SFRP2 in OS specimens. We found that SFRP2 mRNA was significantly decreased and methylation of SFRP2 gene was significantly increased in malignant OS tumors as compared to the paired adjacent non-tumor tissue. Moreover, SFRP2 expression was significantly decreased in the malignant OS cell lines, SAOS2, MG63, and U2OS, but not in the primary osteoblast cells. The demethylation of SFRP2 gene by 5′-aza-deoxycytidine (5-aza-dCyd) in OS cell lines restored SFRP2 expression, at both mRNA and protein levels, and suppressed cell invasion. Furthermore, the demethylation of SFRP2 gene appeared to inhibit nuclear retention of a key Wnt signaling factor, β-catenin, in OS cell lines. Together, these data suggest that SFRP2 may function as an OS invasion suppressor by interfering with Wnt signaling, and the methylation of SFRP2 gene may promote pathogenesis of OS.


Osteosarcoma (OS) Secreted frizzled-related proteins (SFRPs) Methylation 5-aza-dCyd Wnt signaling β-catenin Cancer invasion 



This work was supported by National Grant of The Education Department of Liaoning Province (No: L2014336).

Compliance with ethical standards

Conflicts of interest

The authors have declared that no competing interests exist.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Hand SurgeryThe First Affiliated Hospital of Liaoning Medical UniversityJinzhouChina

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