Fig. 6: GPX4 expression and ACSL4 depletion inhibit tumor necrosis and progression.
From: Neutrophil-induced ferroptosis promotes tumor necrosis in glioblastoma progression
a Chromogenic immunodetection of GPX4 in an endpoint LN229TAZ(4SA) tumor section. N necrotic region, CT cellular tumor region. The outlined area is shown on the right. Three animals were examined independently with similar observations. b Kaplan–Meier survival curve of mice implanted with LN229TAZ(4SA) cells transduced with vector or rGPX4. n = 4 mice for each group. Two-sided log-rank test. c Necrosis-to-tumor area ratios of tumors as indicated in b upon reaching same tumor size as measured by bioluminescence imaging. n = 4. Unpaired two-tailed t-test. d Necrosis-to-tumor area ratios of tumors developed from LN229TAZ(4SA) cells transduced with scrambled shRNA (sh-Control; n = 7) or shRNAs targeting ACSL4 (sh #41 n = 7; sh #42 n = 6). Ordinary one-way ANOVA. In c and d, n indicates number of tumors. Each data point represents an animal. Data presented as mean ±  s.e.m. e Kaplan–Meier survival curve of mice implanted with tumors indicated in d. nsh-Control = 6, nsh-ACSL4 #41 = 3, and nsh-ACSL4 #42 = 3. Two-sided log-rank test. n indicates number of mice. f Cytokine arrays of indicated tumor lysates. (1) CCL2, (2) IL6, (3) CXCL1, (4) CXCL family (CXCL1, CXCL2, and CXCL3), (5) IL8, and (6) TIMP2. g Differential expression (analyzed through https://glioblastoma.alleninstitute.org) and predicted activation (analyzed through IPA; right-tailed Fisher’s exact test) of indicated genes. h Expression of indicated genes in GBM subtypes. Data presented as box-and-whisker plots with boxes marking first quartile, median, and third quartile and with whiskers extending 1.5 times the inter-quartile range. Each point represents a tumor (nCL = 199; nMES = 166; nPN = 163). CCL2: PMES-PN = 1.7e-32; PMES-CL = 2.7e-18. CXCL1: PMES-PN = 4.9e-15; PMES-CL = 8.5e-14. IL6: PMES-PN = 1.4e-22; PMES-CL = 4.4e-33. Pairwise t-tests with Bonferroni correction. i Survival of GBM patients showing higher (top 25%) or lower (bottom 25%) expression of indicated genes. Log-rank test. n indicates number of human subjects. In h and i, analysis of TCGA dataset through GlioVis. Scale bars in μm. Source data provided as a Source Data file.
