Extended Data Figure 3. Tumors induce lipid accumulation in metastasis-free livers.
a,b, PLS-DA plots of the lipid species in the livers from B16F10-Tb mice (a) and K7M2-Tb mice (b), compared to their PBS-injected controls. Lipidomics MS data are shown in Supplementary Tables 3 and 4. n=5 mice per group. c,d, Volcano plots showing the significantly (P<0.05) enriched triglyceride species (red) and cholesteryl ester species (blue) in the livers from B16F10-Tb mice (c) and K7M2-Tb mice (d), compared to their PBS-injected controls. n=5 mice per group. e, Statistical analysis of BODIPY staining of livers from murine melanoma B16F1-Tb mice, murine breast cancer 67NR-Tb and 4T1-Tb mice, genetic melanoma-bearing mice, and their respective controls. n=5 mice per group for B16F1, 67NR and 4T1 models; n=14 control and n=10 tumor-bearing mice for the genetic melanoma model. f, Representative H&E staining images of livers from KPC mice. Liver metastasis was observed in 20-week, but not 14-week tumor bearing mice. g, Statistical analysis of BODIPY staining of the livers from 14-week PDAC tumor-bearing mice, compared to non-PDAC mouse controls. n=3 mice per group. h, Schematic representation of murine tumor models utilized in this study. SK-MEL-192 cells were subcutaneously injected into nude (outbred) mice. Patient-derived xenograft (PDX) models of osteosarcoma were generated by transplanting surgically excised primary tumor specimens from clinical patients into NOD/SCID/IL2Rγnull (NSG) mice. Age and sex-matching mice injected with PBS were used as controls of these experimental murine models. i, Representative H&E staining images of the livers from SK-MEL-192-Tb and control. This experiment was repeated three times independently with similar results. j, Representative MRI images showing lung metastasis, but not liver metastasis detected in osteosarcoma-PDX (OS-PDX) mouse models. This experiment was repeated seven times independently with similar results. k, Statistical analysis of BODIPY staining of livers from human melanoma SK-MEL-192-Tb mice, osteosarcoma-PDX tumor-bearing mice, and their respective controls. n=6 mice per group for SK-MEL-192 model; n=5 control and n=7 tumor-bearing mice for osteosarcoma-PDX model. l, Measurement of body mass index (BMI) of PDAC patients and control subjects with benign lesions. n=14 control subjects and n=16 PDAC patients. Scale bars, 500 μm for (f) and 200 μm for (i). P values were determined by the two-tailed, unpaired Student’s t-test (c-e,g,k,l). Data are mean ± s.e.m. NS, not significant.