Fig. 4: Disrupting BACE1 in U937-derived Macrophages Suppresses Tumor Growth in GBM Xenografts Derived from GSCs Co-transplanted with the Macrophages.

a, A schematic illustration showing the co-transplantation experiment to examine the effect of BACE1 disruption in U937-M2 macrophages on tumor growth in GBM xenograft models. Briefly, human GSCs (CCF-DI315) expressing luciferase in combination with or without U937-derived macrophages expressing shBACE1 (shBACE1: #1 or #2) or non-targeting control (shNT) were co-transplanted into NSG mouse brains through intracranial injection (GSCs: Macrophages = 1:2). Bioluminescent imaging (IVIS) were performed twice per week to monitor tumor growth. GSCs: Glioma stem cells; ICI: Intracranial injection; Luc: Luciferase; MP: Macrophage.

b,c, In vivo bioluminescent analysis to monitor tumor growth of orthotopic GBM xenografts derived from luciferase-expressing GSCs (CCF-DI315) co-transplanted with or without U937-derived macrophages expressing shBACE1 (shBACE1: #1 or #2) or shNT (control) in mice. Representative bioluminescent images (b) on the indicated days are shown. Quantifications (c) show the mean bioluminescence of GBM xenografts derived from GSCs (CCF-DI315) alone, GSCs plus shNT-expressing U937-derived macrophages, or GSCs plus shBACE1-expressing U937-derived macrophages on Days 7, 14, and 21. Data are shown as means ± SEM. n = 5 mice per group. Statistical significance was determined by one-way ANOVA analysis; p values are indicated on the figure.

d, Kaplan-Meier survival curves of the mice bearing GBM xenografts derived from GSCs (CCF-DI315) alone, GSCs plus U937-derived macrophages expressing shNT, or GSCs plus U937-derived macrophages expressing shBACE1 (shBACE1: #1 or #2). n = 5 mice per group. Log-rank analysis was used to assess the significance; p values are indicated on the figure.