Abstract
Glioblastoma (GBM) is an aggressive tumor with a dismal prognosis. Neural stem-like cells contribute to GBM’s poor prognosis by driving drug resistance and maintaining cellular heterogeneity. GBM neural stem-like cells express high levels of brain fatty acid-binding protein (FABP7), which binds to polyunsaturated fatty acids (PUFAs) ω-6 arachidonic acid (AA) and ω-3 docosahexaenoic acid (DHA). Similar to brain, GBM tissue is enriched in AA and DHA. However, DHA levels are considerably lower in GBM tissue compared to adult brain. Therefore, it is possible that increasing DHA content in GBM, particularly in neural stem-like cells, might have therapeutic value. Here, we examine the fatty acid composition of patient-derived GBM neural stem-like cells grown as neurosphere cultures. We also investigate the effect of AA and DHA treatment on the fatty acid profiles of GBM neural stem-like cells with or without FABP7 knockdown. We show that DHA treatment increases DHA levels and the DHA:AA ratio in GBM neural stem-like cells, with FABP7 facilitating the DHA uptake. We also found that an increased uptake of DHA inhibits the migration of GBM neural stem-like cells. Our results suggest that increasing DHA content in the GBM microenvironment may reduce the migration/infiltration of FABP7-expressing neural stem-like cancer cells.
Highlights
Glioblastoma is the most common primary brain cancer in adults [1,2]
As our previous results indicate that an increased docosahexaenoic acid (DHA):arachidonic acid (AA) ratio inhibits GBM cell migration [34], we compared the fatty acid profiles of GBM neural stem-like cells versus GBM adherent cells, and the effect of DHA and AA supplementation on their respective fatty acid profiles
We first examined the expression of FABP7, an established GBM neural stem-like cell marker [40], in our paired
Summary
Glioblastoma (grade IV astrocytoma) is the most common primary brain cancer in adults [1,2] It is a highly aggressive and deadly cancer, with a median survival time of. Resistance to treatment is due in part to the invasion of surrounding brain parenchyma by GBM cells, suggesting that targeting the infiltrative properties of GBM cells might be an effective therapeutic strategy [5]. In addition to their infiltrative nature, GBMs are highly heterogeneous tumors at both the cellular and molecular levels, adding an additional level of complexity to the effective targeting of these tumors [6,7]. Dysregulation of lipid metabolism has been associated with maintenance of GBM stemness and poor survival [14,15]
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