Fig. 1 | Nature Communications

Fig. 1

From: The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells

Fig. 1

27HC is a biochemical mediator of the effects of obesity and elevated cholesterol on breast cancer metastasis. a A high-cholesterol diet (HCD) increases spontaneous metastasis of murine ER-negative Met1 cells (N = 10 each). b Mice fed a high-cholesterol diet (HCD) exhibit increased lung colonization of i.v. grafted Met1 mammary tumors (CD N = 7, HCD N = 8). c A high-fat diet (HFD) increases lung colonization of murine E0771 i.v. grafts in APOE3 mice (i.v. graft of cells). Pretreatment for 7 days prior to the graft and continued treatment throughout the study with daily placebo or atorvastatin (statin, 40 mg/kg) by oral gavage reduced metastatic colonization. Representative images of iRFP-expressing E0771 colonies (depicted as black) within the lungs are presented above quantified data (control diet (CD) placebo N = 11, statin N = 7, HFD placebo N = 8, statin N = 7, scale bar indicates 5 mm). d Chronic administration of exogenous 27-hydroxycholesterol (27HC) increases spontaneous metastasis to the lung as measured by relative fluorescence (inset) without impacting growth rate of the primary tumor (N = 3). e Metastatic effects of a HCD in MMTV-PyMT mice requires conversion to 27HC by CYP27A1 (wild-type CD N = 8, HCD N = 14, CYP27A1−/− CD N = 3, HCD N = 9). Quantitative RT-PCR for PyMT transcript within the lung is presented in the graph and used to quantify metastasis since its expression should be restricted to mammary epithelial cells. f Chronic treatment with a small molecule inhibitor of CYP27A1, GW273297X (GW297X) decreases colonization of lung tissue from Met1 i.v. grafts (N = 4 each). g Lung colonization from E0771 i.v. grafts in APOE3 mice is increased by a HFD, but attenuated in mice chronically treated with GW297X (CD placebo N = 5, GW297X N = 3, HFD placebo N = 7, GW297X N = 6). Results are depicted as mean +/− SEM. Lines and asterisks denote statistical differences between groups (p < 0.05). [a, b, d, f: Unpaired two-tailed student’s t-test. c, e, g: One-way ANOVA followed by a Student Newman-Keuls multiple comparison test]

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