Abstract 6824: Secretion of MAGE-A3 and MAGE-A4 in cell lines and lung cancer

Abstract Melanoma-associated antigen gene A (MAGE-A) family of proteins have previously been shown to express in a variety of tumors, having different roles in cancer pathogenesis. MAGE-A3 and MAGE-A4 have both been shown to inhibit the p53 pathway which leads increased cell growth by stopping apoptosis. Both of these proteins have been associated with cancer progression and poor prognosis. In our studies, we have evaluated multiple MAGE-A3 and MAGE-A4 antibodies using CytoSections. While previous research had only pointed to these proteins being intracellular, our overexpression studies in the development of CytoSections indicated that some MAGE-A proteins were secreted. In this study, ELISA binding assays corroborated that MAGE-A3 and MAGE-A4 were secreted from cells overexpressing these proteins, and serum MAGE-A4 was detected in 24% of lung cancer patients. Flow cytometry data was then collected to see that exogenous MAGE-A proteins were binding to cells in a pattern consistent with secretion data from IHC experiments. Variants of MAGE-A4, differing by only a handful of amino acids, showed very different levels of secretion from one another. MAGE-A3 and MAGE-A6 share 95% homology and were also extremely different in secretion shown between IHC, flow cytometry, and ELISA. This study validates that certain members of the MAGE-A family are secreted from cells. Citation Format: Bailey Gilmore, Dehe Kong, Rachel Gonzalez, Jina Yom, Andy Han, Tianli Qu, Alex Strom, Xiaoxiao Zhao, Eden Zewdu, Hailey Guo, Zhaoying Guo, Ranran Zhang, Xiaomin Hu, Qi Ren, Xuan Liu, Wei Fu. Secretion of MAGE-A3 and MAGE-A4 in cell lines and lung cancer [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 6824.