Midkine as a prognostic marker and therapeutic target in osteosarcoma. H. Maehara¹, T. Kaname^2,3, K. Yanagi², I. Ohwan¹, K. Naritomi^2,3, F. Kanaya¹. 1) Department of Orthopedics, University of the Ryukyus, Nishihara, Okinawa, Japan; 2) Department of Medical Genetics, University of the Ryukyus, Nishihara, Okinawa, Japan; 3) Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology, Kawaguchi, Japan.
   A heparin-binding growth factor, midkine and its truncated form are involved in generation and progression of various tumors. It is, however, the relationship between midkine and osteosarcoma is unclear yet. We show midkine is overexpressed in osteosarcoma patients and its intensity correlated with their prognosis (p<0.05). No truncated form of midkine was observed in any osteosarcoma cells, which may suggest that there is no association between intronic mutation of midkine gene and tumorigenesis of osteosarcoma. Treatment with functional antibodies against midkine has inhibited cell growth between approximately 20% and 60% in osteosarcoma cell lines, 9N2, 3N1, Saos2 and Nos1 in vitro. Reducing of midkine expression in those cells by RNAi gave the same results. Our findings suggest that midkine will be used as a prognostic marker and will be one of the strong candidate for therapeutic target for osetosarcomas.