Abstract 1736: Role of brain fatty acid binding protein in glioblastoma microtube formation

Abstract

Abstract Glioblastoma (GBM) is a highly infiltrative brain cancer with a dismal prognosis. Conventional treatment using surgery, radiation therapy, and chemotherapy (usually temozolomide) invariably fails. GBM microtubes, which are ultra-long membrane-enclosed protrusions, are associated with therapy resistance and are believed to function by forming multicellular communication networks. Growth-associated protein GAP43 is an important protein for GBM microtube formation. Although lipids are important for GBM progression, the roles of lipid chaperones such as the fatty acid-binding proteins (FABPs) are not well understood. FABPs are involved in fatty acid uptake from the microenvironment and intracellular transport of fatty acids. Brain fatty acid binding protein (FABP7) is highly expressed and is associated with a poor prognosis in GBM. FABP7 levels increase in therapy-resistant GBM cells, suggesting that FABP7 provides a cancer cell survival advantage when GBMs are treated with conventional therapy. FABP7 has a high affinity for polyunsaturated fatty acids (PUFAs), such as omega-3 docosahexaenoic acid (DHA) and omega-6 arachidonic acid (AA), both of which are abundant in brain. Previous studies have shown a correlation between FABP7 expression, increased neural stem cell properties, and increased cell migration in glioblastoma cells, especially when FABP7 is bound to AA. We have recently found that FABP7 is expressed in microtubes, leading to the hypothesis that FABP7 along with its fatty acid ligands can be transported to sites distant from the main tumor mass through these connecting tubes. We are studying the mechanism of action of FABP7 in microtubes by: (i) examining the effect of DHA and AA, as well as FABP7 inhibition on microtube formation and cell migration, and (ii) using both neurosphere cultures and animal models of glioblastoma to investigate the pathways that are activated by FABP7. Our results to date support the use of FABP7 inhibitors to sensitize therapy-resistant cells as part of the standard-of-care for the treatment of GBM patients. Citation Format: Won-Shik Choi, Caitlin Mak, John M. Githaka, Darryl Glubrecht, Pureunsol Jeon, Roseline Godbout. Role of brain fatty acid binding protein in glioblastoma microtube formation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1736.