Abstract 5171: Expression and function of Snail2 in osteosarcoma

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Purpose: Snail2 is a well established regulator of EMT in malignant epithelial tumors, however in sarcomas it is not known if this protein is present and contributes to tumor progression. Here we examine the expression of Snail2 in clinical cases of one type of sarcoma; osteosarcoma. We hypothesize that Snail2 is expressed in osteosarcomas and that this expression correlates with tumor grade. In addition, we also hypothesized that Snail2 promotes metastasis in osteosarcomas. Experimental design: Snail2 localization was determined in clinical biopsies of different grades of canine osteosarcomas using immunohistochemistry. The function of Snail2 in OS was evaluated using stable human and canine OS cell lines in which loss of function was achieved using small interfering RNA (siRNA) and gain of function using over-expression vectors. These lines were used to assess changes in cell motility and invasion using in vitro assays. Results: Nuclear Snail2 staining was observed in all cases of osteosarcoma examined. Ordinal logistic regression analysis revealed that elevated Snail2 expression was significantly (P=0.014) correlated with tumor grade. Cell lines of canine (D-17) and human (Saos-2) osteosarcoma stably transfected with Snail2 siRNA showed a loss of osteoblastic morphology becoming flattened whereas those overexpressing Snail2 appeared more spindle shaped. Scratch assays showed that motility of osteosarcoma cells was correlated with levels of Snail2 expression. Conclusion: This is the first time Snail2 has been associated with any sarcoma and this study shows that Snail2 may be a useful prognostic marker for osteosarcoma. In addition, it indicates that Snail2 may play a role in osteosarcoma metastasis. Thus it may be a potential target for clinical intervention in this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5171. doi:10.1158/1538-7445.AM2011-5171