Abstract 4465: Galectin-1 regulates CD147 and downstream pathways critical for glioma progression

Abstract

Abstract Galectin-1 (Gal-1) is an important protein for glioma progression and glioma stem cell maintenance. Gal-1 may act through CD147, a potential Gal-1 receptor. CD147, also known as Basigin or extracellular matrix metalloproteinase inducer (EMMPRIN), is a transmembrane glycoprotein highly expressed in various cancer cells. An analysis utilizing the Gliovis database and encompassing 667 Glioblastoma Multiforme (GBM) patients segregated based on median CD147 expression levels delineated cohorts with above-median (n=339) and below-median (n=328) CD147 expression. Kaplan-Meier survival curves unveiled a significant association between heightened CD147 expression and reduced overall survival (OS) in this patient population. Experimental approaches employing immunoblotting and immunohistochemistry techniques on shGal-1 treated cell lysates and mouse brain samples exhibited decreased CD147 expression compared to respective controls. Additionally, immunocytochemical studies corroborated an augmented colocalization of Gal-1 and CD147, with a subsequent reduction in this association following shGal-1 treatment. Next, we used AC-73, a selective CD147 inhibitor, to determine the levels of CD147 and Gal-1. Treatment with 20μM AC-73 and siRNA for CD147 showed reduced CD147 levels in GSC33 and GSC20 cells while maintaining unaltered Gal-1 expression. Inhibiting CD147 did not affect Gal-1 levels, further suggesting Gal-1 acts upstream. CD147 activates matrix metalloproteinase-9 (MMP9), and CD147 knockdown reduced MMP9 levels, elucidating a Gal-1-CD147-MMP9 pathway. Overall, Gal-1 appears to act upstream of CD147 to regulate MMP9, integrins, and other factors important for glioma progression. Further elucidation of these pathways will provide insights into glioma biology and potential therapeutic targets. Citation Format: Maheedhara R. Guda, Andrew J. Tsung, Swapna Asuthkar, Kiran Velpula. Galectin-1 regulates CD147 and downstream pathways critical for glioma progression [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 4465.