Supplementary Figure 5: IMPDH activity is critical for GBM to promote growth in vivo.
From: IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma
a, Growth of murine GSC in brain tissue is inhibited by MPA in the presence of physiologically relevant guanosine. GFP-expressing murine GSC brain explant slices in immunocompetent mice were cultured with or without 10 μΜ MPA and 1 or 10 μM guanosine. Scale bar indicates 300 μm. Presented data are from 3 out of 4 different mice. Scale bar indicates 300 μm. b, MMF administration suppresses GBM growth. Kinetics of tumor size and mouse weight corresponding to Fig. 4f are shown. Data are presented as mean+s.d. Vehicle (n=3), MMF treatment (n=5). c, Depletion of IMPDH2 gene decreases tumor progression of GBM. Kinetics of tumor size corresponding to Fig. 4g is shown. Data are presented as mean+s.d. from Control (n=6), IMPDH1 KO (n=5), IMPDH2 KO (n=6), IMPDH DKO (n=7) groups. d, Compensatory upregulation of IMPDH1 in IMPDH2 KO in GBM growing in the brain. GFP-tagged luciferase expressing IMPDH2 KO U87MG cells and parental U87MG were implanted in the brain. Bioluminescence imaging showed IMPDH2 KO tumor growth at 3 weeks. The dissected IMPDH2 KO tumor cells from the brain dramatically increased IMPDH1 protein levels. Presented data are from n=2 different animals. Scale bar indicates 200 μm.
