WNT SIGNALING SWITCH: DYNAMICS AND ROLE IN OSTEOSARCOMA DEVELOPMENT

Wnt signaling pathways are evolutionary conserved among metazoans playing a pivotal role in regulation of cell fate decisions in normal and cancerous cells. Previous studies revealed a “switch” from canonical to non-canonical Wnt pathways in some cancer types, a phenomenon which led to increased proliferation, invasiveness and metastasis. Mesenchymal stem cells (MSCs) are present in tumor microenvironment and play a role in tumor progression. However, the role of Wnt switch in progression of sarcomas is not yet understood and the effects of MSCs on these processes are unknown. In the current in vitro study, Wnt signaling pathway is investigated in OS cells which were co-cultured with MSCs. The results revealed that OS cells in co-culture with MSCs showed reduced adhesion and differentiation, and increased tumorigenicity and metastatic characters. In addition, Wnt signaling activity was enhanced, implying on elevation of non-canonical Wnt signaling activity. The switch up-regulated a plethora of tumor related genes and its down-stream target gene c-Myc, implying on a pivotal role in tumorigenicity. We suggest that within the unique bone microenvironment this phenomenon is enhanced.