Abstract 4133: Suppressed B7-H3 expression reduces glycolytic capacity and sensitizes tumor cells to anti-cancer agents

Abstract

Abstract B7 family proteins are important immune response regulators, and can mediate oncogenicity-related signals and support cancer development. We have prevously shown that the B7-H3 protein promotes tumor cell invasion, proliferation and mestastasis, and increases resistance to chemotherapy. Now we have used human breast and melanoma cancer cell lines with different expression levels of B7-H3 to further evaluate the role of B7-H3 on the sensitivity to anticancer compounds. B7-H3 knockdown tumor cells showed enhanced chemosensitivity compared to their B7-H3 expressing counterparts, as well as increased inhibition to treatment with compounds that target proteins in the PI3K/AKT/mTOR- and MAPK-pathways (Nunes-Xavier et al. in revision). Treatment of control cells with an anti-B7-H3 monoclonal antibody resulted in similar sensitization, whereas B7-H3 overexpressing cells and xenografts were less sensitive. Of note, knockdown of B7-H3 decreased and B7-H3 overexpression increased the glycolytic capacity of the breast cancer and malignant melanoma cells. In conclusion, we have demonstrated a previously unknown relationship between B7-H3 expression and glycolysis in tumor cells, and found that B7-H3 confers resistance to also to pathway inhibiting agents. The results provide novel insights into the function of B7-H3 in cancer, and suggest that targeting of B7-H3 expression may be a promising alternative to improve current anticancer therapy. Citation Format: Caroline E. Nunes-Xavier, Karine Flem Karlsen, Tove Øyjord, Ming Tan, Øystein Fodstad. Suppressed B7-H3 expression reduces glycolytic capacity and sensitizes tumor cells to anti-cancer agents. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4133.