Carbonic anhydrase IX enhances tumor cell proliferation and tumor progression in osteosarcoma

Kazuma Okuno,1,2 Takao Matsubara,1 Tomoki Nakamura,1 Takahiro Iino,1 Takuya Kakimoto,1 Kunihiro Asanuma,1 Akihiko Matsumine,1,3 Akihiro Sudo1 1Department of Orthopedic Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan; 2Department of Orthopedic Surgery, Ise Red Cross Hospital, Ise, Japan; 3Department of Orthopedic Surgery, Fukui University Graduate School of Medicine, Fukui, Japan Purpose: We investigated the effect of carbonic anhydrase IX (CA IX) inhibitor under hypoxia and normoxia in SaOS2 human osteosarcoma cell line. We also evaluated the expression of CA IX in 27 patients diagnosed with osteosarcoma.Materials and methods: CA IX expression in SaOS2 cells cultured under different oxygen tensions was analyzed by Western blotting. To evaluate the effect of CA IX inhibitor, MTS cell viability assay was performed after cells were treated with various concentrations of doxorubicin with or without a CA IX inhibitor. Finally, CA IX expression in patient-derived osteosarcoma samples was evaluated by immunohistochemistry.Results: Treatment with CA IX inhibitor significantly suppressed cell proliferation and migration under hypoxic conditions. CA IX expression was observed in 81% of 27 patients. The 5-year survival rates in patients with high and low stain scores were 43.8% and 81.8%, respectively.Conclusion: CA IX inhibitors have the potential to suppress cell proliferation, migration, and chemoresistance. Keywords: hypoxia, osteosarcoma, carbonic anhydrase IX, inhibito