Abstract 557: Clofarabine inhibits U87MG glioblastoma cell line proliferation through CD99 signaling pathway

Abstract The present work aimed to test the efficacy of clofarabine in glioblastoma (GBM) cells that express high levels of CD99. GBMs are the most malignant with the poorest prognosis among tumors of the central nervous system. Patients have a median survival of 12 to 15 months despite surgical, radio, and chemotherapy. CD99 is a cell surface receptor overexpressed in several types of tumors, including GBMs, justifying the interest of studies in CD99 as a possible therapeutic target. Our group has previously demonstrated that knockout of CD99 in the U87MG GBM cell line promoted a decrease in cell adhesion, migration, and invasion. Clofarabine is a third-line drug used in the treatment of refractory/relapsed childhood acute lymphoblastic leukemia. It is a purine analog that is transported into intracellular space, phosphorylated, and incorporated into DNA chain, inhibiting DNA synthesis and ultimately inducing cell death by apoptosis. The clofarabine effect has also been demonstrated in cells from solid tumors, such as breast, gastric, and bladder. Clofarabine action on the proliferation of Ewing sarcoma cells in vitro and in vivo was proved to be by direct binding to CD99 and independent of the drug internalization. In addition, clofarabine also had an effect on cells from other tumor types that express CD99. The present work demonstrated the significant action of clofarabine on the high CD99-expressing U87MG cells by inhibiting cell proliferation, adhesion, and migration, and by inducing cell cycle arrest and apoptosis. U87MG cells knocked out for CD99 expression were more resistant to clofarabine action on proliferation. RNAseq analysis of U87MG cells treated with clofarabine and compared to control showed downregulated genes involved in cell cycle regulation and mitosis, while upregulated genes were enriched in extracellular proteins, cell adhesion, locomotion, p53 signaling pathway, and apoptosis. Our data indicates clofarabine as a potential CD99 inhibitor to treat GBM patients. Citation Format: Camila Cristina de Souza, Roseli da Silva Soares, Antonio Marcondes Lerario, Suely Kazue Marie, Sueli Mieko Oba-Shinjo. Clofarabine inhibits U87MG glioblastoma cell line proliferation through CD99 signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 557.