Characterization of R and VR tumors grafted in mice.

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Characterization of R and VR tumors grafted in mice. Characterization of R and VR tumors grafted in mice. (A, B) Comparative growth curve of R, VdR, and VR J2A tumors (n = 7, t test and ANOVA, ***P < 0.001) in nude (A) and immunocompetent C57BL/6 (B) mice. (C) Metabolomics analysis of R and VR H1 tumors by LC-MS (n = 6) showing the hierarchical cluster of metabolic pathways according to cell types. Scaling is in unit of variance (mean/squared root of SD). (D) Metabolomics analysis of R and VR J2A tumors by NMR (n = 7) displaying the relative enrichment in metabolites in R (top panel) versus VR (bottom panel) cell lines. Orthogonal Projections to Latent Structures Discriminant Analysis loading plot are color-coded according to the correlation coefficients of each signal with the predictive component of the tumor samples. Metabolites with positive intensities are in higher concentrations in R samples, whereas metabolites with negative intensities are in higher concentrations in VR samples (P value of 0.008). (E) Transcriptomic analysis of J2A tumors (n = 5). BubbleGUM analysis displaying enrichment of gene sets on the pairwise comparisons of R, VdR, and VR tumors (NES, normalized enrichment score). The gene sets were downloaded from MSigDB (Broad Institute). The bubble area is proportional to the normalized enrichments score (NES) calculated by GSEA. The intensity of the color corresponds to the statistical significance of the enrichment. (F, G) Typing of the differentiation grade of J2A tumors by in situ collagen (Masson trichrome) versus hematoxylin staining (F) or qRT–PCR analysis of collagen 1 and caveolin 1 transcripts (n = 5, unpaired t test, *P < 0.05; **P < 0.01) (G). Lac, lactate; Glc, glucose; GSH, glutathione; Tau, taurine; GPC, glycerophocholine; FA, fatty acids; and UFA, unsaturated FA. Caroline Giessner et al. LSA 2018;1:e201800073 © 2018 Naquet et al.