Abstract 1630: Effects of rhBMP-2 on osteosarcoma tumorigenesis

Abstract Introduction: Osteosarcoma (OS) is the most common primary bone malignancy in children and young adults. Complete surgical extirpation of bulk tumor is essential to successful treatment of OS. While historically ablative surgery such as amputations were the mainstay of treatment, wide excision has been shown to provide equivalent survival results, permitting for limb-salvage surgery in over 90% of cases. Following tumor resection, structural allograft bone is often employed to reconstruct the involved extremity. Bone Morphogenetic Protein-2 (BMP-2), a member of the TGF beta superfamily, possesses tremendous osteoinductive potential and could theoretically be used to promote bone healing but has been historically contraindicated due to concern it may stimulate residual tumor. To date, the role of BMP-2 in OS remains unclear and its effect on OS remains controversial. The purpose of this investigation is to evaluate the effect of exogenous recombinant human BMP-2 (rhBMP-2) on osteosarcoma. We hypothesize that exposure of osteosarcoma to rhBMP-2 will not stimulate tumor growth or development. Methods: Functional assays were performed using five standard osteosarcoma cell lines (143B, MG-63, SaOS-2, U20S, and HOS) and three patient derived xenograft cell lines (OS17, OS31, LM7). The concentration of rhBMP-2 utilized varied between 0.5 to 2 μg/ml. Motility (random migration) was measured by wound healing scratch assay. Migration (both haptotaxis and chemotaxis) was quantitatively measured using Boyden Chamber assay. Invasion was also measured using Boyden chamber over which a thin layer of extracellular matrix is applied. Comparison between different concentrations of rhBMP-2 upon different time points on osteosarcoma cell lines and characterizations are completed and underway. Results: Preliminary findings suggest that exogenous rhBMP-2 does not increase the ability of osteosarcoma cells to migrate and invade in all tested lines (143B, MG-63, OS17). Quantitative migration decreases with increasing concentration of rhBMP-2 over a 5-hour time course in all tested lines (143B, SaOS-2, MG-63, OS17). Invasion did not increase with increasing rhBMP-2 concentration in any tested line (143B, SaOS-2, OS17). Conclusions and Future Directions: Preliminary results support the contention that exposure of osteosarcoma to exogenous rhBMP-2 does not increase in vitro tumorigenesis. In fact, findings suggest that rhBMP-2 may have a protective effect in that tumor migration decreases following exposure. Continued characterization using additional tumor lines is ongoing. Citation Format: Sajida Piperdi, David Geller, Amy Park, So Hak Chung, Richard Gorlick. Effects of rhBMP-2 on osteosarcoma tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1630. doi:10.1158/1538-7445.AM2015-1630