Fig. 2.
SXC-expressing gliomas induce peritumoral neuronal cell loss, edema, and decreased survival. (A) Immunofluorescence of nuclei (Dapi, white), peritumoral neurons (NeuN, green), and astrocytes (GFAP, magenta) in cortices implanted with SXC-expressing (GBM22) and non-SXC-expressing (GBM14) gliomas. Inset, 2.5x magnification; scale bars, 50 μm. (B) Peritumoral NeuN+ neuron quantification in the SXC-expressing (red) and non-SXC-expressing (blue) gliomas (n=3 animals per condition). Means ± SEM; ANOVA, Tukey’s post-hoc test, *P<0.05, **P<0.01, ***P<0.0001. (C) Kaplan Meier plot of survival of tumor-bearing mice, days after injection for the SXC-expressing (GBM22, n=14 animals; GBM1066, n=10 animals) versus non-SXC-expressing (GBM14, n=15 animals; GBM39, n=16 animals) gliomas. (D) Representative H&E immunostaining of intracranially implanted SXC-expressing (GBM22; n=3 animals) and non-SXC-expressing (GBM14; n=3 animals) gliomas, highlighting less well defined borders of SXC-expressing gliomas, with finger-like projections invading into surrounding brain tissue (T = tumor, PT = peritumoral tissue; white arrowheads, tumor border). Scale bar, 100 μM. (E) Representative electron microscopy (EM) images showing cell morphology of SXC-expressing (GBM22, red; n=2 animals; 78 images analyzed) and non-SXC-expressing (GBM14, blue; n=2 animals; 46 images analyzed) intracranial gliomas. Tumoral and peritumoral edema (white areas, highlighted by black arrowheads) is apparent between the elaborately wound cellular processes of GBM22 cells. Less abundant, localized edema in GBM14 glioma-bearing cortex with more easily distinguished cell borders (right). GC = glioma cell(s)/processes (green), EC = endothelial cell (purple), BV = blood vessel, black arrowhead = edema. Scale bar, 2 μM.