Wnt5a Induces Tumorigenic Behaviors of Enamel Epithelium Cell

Objective: The Wnt signaling pathways play essential roles during tooth formation. Wnt5a expression is specifically found in mesenchyme during the early stages of tooth development while its expression has not been detected in enamel epithelium. Interestingly, we previously demonstrated that high Wnt5a expression was detected in the abnormal epithelial component of human ameloblastomas using microarray and immunohistochemistry approaches. This observation led us to hypothesize a role for Wnt5a in modulating tumorigenic behavior of enamel epithelium cells. Methods: We established the enamel organ cells (LS-8) derived stable clones expressing high and low levels of Wnt5a by sense and antisense techniques. Effect of Wnt5a on transformation of enamel epithelium cell behavior was investigated in these stable clones by cell proliferation, focus formation and soft agar assay. We also monitored the influence of Wnt5a on cell migration by scratch wound assay. Results: We demonstrated that Wnt5a overexpression is associated with several altered growth properties that are characteristic of tumorigenic cells. The sense transfected cells show less growth factor dependence when cultured in serum reduced condition. Wnt5a overexpressed clones are capable of forming foci after confluence and forming colonies in soft agar, reflecting loss of contact inhibition and loss of anchorage dependent growth. Wnt5a also increases cell migration in enamel epithelial cells. Conclusion: Our results suggested that Wnt5a induced several tumorigenic behaviors and could play an important role in tumorigenesis of enamel epithelium as found in odontogenic tumors.

This work was supported by NIDCR grant#DE016079