Osteosarcoma (OS) is a primary malignant tumor of bone that typically presents in the second decade of life and has poor prognosis especially in metastatic cases. Wnt signaling has been shown to contribute to pathogenesis of tumors such as colon cancer and malignant melanoma. Wnt signaling controls normal bone formation during embryogenesis, hence a potential role of Wnt signaling in OS pathogenesis may exist. We surveyed the expression of Wnts, their receptors frizzled (Fz) and LDL receptor like proteins and Wnt inhibitors (SFRPs) in four OS cell lines by RT-PCR. MG63 and HOS are human osteosarcoma cell lines. K7M2 is a mouse metastatic OS cell line that is derived from K12 a non-metastatic mouse OS cell line. In both human OS cell lines we detected Wnt-2b, Wnt-5a, sFRP4, Fz7, LRP5, and LRP6 expression. In the mouse OS cell lines, Wnt-7b and sFRP4 were detected in K7M2, but not detected in K12. In both K7M2 and K12 we detected Wnt-2, Wnt-3, Wnt-5a, Wnt-8a, Wnt-15, Fz-5, LRP5 and LRP6 expression. These results provide evidence that Wnt ligands and their receptors (Fzs and LRP) are expressed in OS cell lines. Western blot analysis has also shown that the 4 OS cell lines studied can induce cytoplasmic β-catenin by Wnt activation. Therefore, an active autocrine Wnt signaling may contribute to OS pathogenesis. Further more, Wnt-10b PCR product was 230 base pairs smaller, than expected in K7M2. Sequencing of the Wnt-10b PCR product showed that, K7M2 Wnt-10b was missing exon 3. Preliminary studies of Wnt-10b and OS have shown a trend of decrease protein expression of Wn-10b in the metastatically active OS cell lines. This finding suggests that Wnt-10b expression in OS may provide a more differentiated state and protect against metastasis.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]