Fig. 5: Metabolic alterations at the systemic level induced by liver cancer in a xenograft mouse model.
From: Spatial isotope deep tracing deciphers inter-tissue metabolic crosstalk
a Scheme of in vivo deep U-13C glucose tracing in tumor-bearing mice. Created in BioRender. Li, X. (https://BioRender.com/rq6a86p). b H&E-stained image of a tumor section and ×100 magnified H&E-stained images of tumor microregions derived from a HepG2 subcutaneous xenograft mouse infused with U-13C-glucose; scale bar = 2 mm for the whole tissue section, scale bar = 20 μm for the magnified images (left). Images are representative of at least three independent experiments. T1, proliferating areas; T2, necrotic areas; T3, stromal areas. AFADESI-MS images of the isotopologues of glucose, lactate, succinate, acetylcarnitine, glucosyl-glycerol, proline, malate and glutathione across the tumor (right). Intensity shown as relative abundance (normalized to 100%). c Normalized labeling fraction of representative metabolites in the tumor proliferation zone, stroma, and necrotic region, as calculated by MSITracer. Statistics were calculated using one-way ANOVA and post hoc Tukey’s correction. Data are mean ± SD (n = 9; 3 biological replicates, each with 3 independent regions selected from each slice). *p < 0.05, **p < 0.01, and ***p < 0.001. Adjusted p values for comparisons reaching statistical significance are provided in Supplementary Table 2. d AFADESI-MS images of glutamate and glutamine isotopologues M2, M3, and M4 in tumors following U-13C glucose infusion. Intensity shown as relative abundance (normalized to 100%). e, Labeling fingerprints of representative metabolites in tumors, as calculated by MSITracer. Data are mean ± SD (n = 9; 3 biological replicates, each with 3 independent regions selected from each slice). f Heatmap of the differences in the normalized labeling of UDP-GIcNAc isotopologues across organs between normal and tumor-bearing mice. Each data point represents the means of normalized labeling from three biological replicates. Source data are provided as a Source Data file. g Illustration of the impact of tumor burden on the HBP pathway in host organs and the glutamine communication between the host and the tumor. Created in BioRender. Li, X. (https://BioRender.com/yewga37).
