Extended Data Fig. 1: High fat diet enhances several fatty acids, while during pre-metastatic niche formation only palmitate increases.
a. Fraction of free fatty acids (gray) over total fatty acid content (black) of the liver interstitial fluid of healthy BALB/c mice (n = 7). b. Mouse weight gain upon high fat or control diet over the course of the experiment. Data are presented as mean ± SEM (n =60 mice). Mixed-effects analysis with Sidak’s multiple comparisons. c. Palmitate and oleate abundance in the lung interstitial fluid of BALB/c mice after 16 weeks on control (CD) or high fat (HFD) diet (n = 11 mice). Data are presented as mean ± SEM of absolute concentration measured by mass spectrometry. Unpaired two-tailed t-tests with Welch correction. d. Palmitate and oleate abundance in the liver interstitial fluid of BALB/c mice after 16 weeks on CD or HFD diet (n = 8 mice). Data are presented as mean ± SEM of absolute concentration measured by mass spectrometry. Unpaired two-tailed t-tests with Welch correction. e. Schematic illustration for experimental pre-metastatic niche formation procedure. CM, control media; TCM, tumor conditioned media; i.v. intravenous. f. Changes in gene expression in lung populations upon TCM injection relative to CM injections, for genes whose upregulation has been previously linked to pre-metastatic niche formation, such as S100a8, S100a9, Mmp988,89 and Tlr3 and Cxcl2 in lung alveolar type II cells88, Tlr4 and Saa3 in lung endothelial cells and macrophages90; Slc2a1, Pdk1, and Ldha in macrophages91, and S100 genes in lung fibroblasts92. The color scale denotes log2 fold changes in TCM vs. CM. g. Relative glucose concentration in the lung interstitial fluid of healthy BALB/c mice exposed to control media (n = 10 mice) or tumor condition media (n = 8 mice). Data are presented as mean ± SEM. Unpaired two-tailed t-tests with Welch correction. h. Granulocytes population (which includes neutrophils) present in the lungs after induction of pre-metastatic niche formation using tumor conditioned media or control media. Data are presented as mean ± SEM (n = 3 mice). Unpaired two-tailed t-tests with Welch correction. i. Palmitate and oleate abundance in the lung (n = 16) and liver (n≥7) interstitial fluid of BALB/c mice injected with control media (CM) or 4T1 tumor conditioned media (TCM) (3 weeks, 3 times/week). Data are presented as mean ± SEM. Unpaired two-tailed t-tests with Welch correction. j. Palmitate concentration in the liver interstitial fluid of healthy (n = 11 mice) or 4T1 tumor-bearing (PT) (n = 19 mice) BALB/c mice. Data are presented as mean ± SEM.
