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

Publication ,  Journal Article
Baek, AE; Yu, Y-RA; He, S; Wardell, SE; Chang, C-Y; Kwon, S; Pillai, RV; McDowell, HB; Thompson, JW; Dubois, LG; Sullivan, PM; Kemper, JK ...
Published in: Nat Commun
October 11, 2017
Published version (DOI) Link to item

Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating hypercholesterolemia, is associated with improved disease-free survival. Here, we show that cholesterol mediates the metastatic effects of a high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or inhibition of CYP27A1, the enzyme responsible for the rate-limiting step in 27-hydroxycholesterol biosynthesis, significantly reduces metastasis in relevant animal models of cancer. The robust effects of 27-hydroxycholesterol on metastasis requires myeloid immune cell function, and it was found that this oxysterol increases the number of polymorphonuclear-neutrophils and γδ-T cells at distal metastatic sites. The pro-metastatic actions of 27-hydroxycholesterol requires both polymorphonuclear-neutrophils and γδ-T cells, and 27-hydroxycholesterol treatment results in a decreased number of cytotoxic CD8+T lymphocytes. Therefore, through its actions on γδ-T cells and polymorphonuclear-neutrophils, 27-hydroxycholesterol functions as a biochemical mediator of the metastatic effects of hypercholesterolemia.High cholesterol is a risk factor for breast cancer recurrence. Here the authors show that cholesterol promotes breast cancer metastasis via its metabolite 27-hydroxycholesterol (27HC) that acts on immune myeloid cells residing at the distal metastatic sites, thus promoting an immune suppressive environment.

Duke Scholars

Yen-Rei Andrea Yu
Author Yen-Rei Andrea Yu Medicine, Pulmonary, Allergy, and Critical Care Medicine
Suzanne E Wardell
Author Suzanne E Wardell Pharmacology & Cancer Biology
Ching-yi Chang
Author Ching-yi Chang Pharmacology & Cancer Biology
J. Will Thompson
Author J. Will Thompson Pharmacology & Cancer Biology
Patrick Sullivan
Author Patrick Sullivan Medicine, Geriatrics
Michael Dee Gunn
Author Michael Dee Gunn Medicine, Cardiology
Donald Patrick McDonnell
Author Donald Patrick McDonnell Pharmacology & Cancer Biology
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Published In

Nat Commun

DOI

10.1038/s41467-017-00910-z

EISSN

2041-1723

Publication Date

October 11, 2017

Volume

8

Issue

1

Start / End Page

864

Location

England

Related Subject Headings

  • Obesity
  • Neoplasm Metastasis
  • Myeloid Cells
  • Mice, Inbred C57BL
  • Mice
  • Hydroxycholesterols
  • Humans
  • Female
  • Cholesterol, Dietary
  • Cell Line, Tumor
 

Citation

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Baek, A. E., Yu, Y.-R., He, S., Wardell, S. E., Chang, C.-Y., Kwon, S., … Nelson, E. R. (2017). The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nat Commun, 8(1), 864. https://doi.org/10.1038/s41467-017-00910-z
Baek, Amy E., Yen-Rei A. Yu, Sisi He, Suzanne E. Wardell, Ching-Yi Chang, Sanghoon Kwon, Ruchita V. Pillai, et al. “The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells.” Nat Commun 8, no. 1 (October 11, 2017): 864. https://doi.org/10.1038/s41467-017-00910-z.
Baek AE, Yu Y-RA, He S, Wardell SE, Chang C-Y, Kwon S, et al. The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nat Commun. 2017 Oct 11;8(1):864.
Baek, Amy E., et al. “The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells.” Nat Commun, vol. 8, no. 1, Oct. 2017, p. 864. Pubmed, doi:10.1038/s41467-017-00910-z.
Baek AE, Yu Y-RA, He S, Wardell SE, Chang C-Y, Kwon S, Pillai RV, McDowell HB, Thompson JW, Dubois LG, Sullivan PM, Kemper JK, Gunn MD, McDonnell DP, Nelson ER. The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nat Commun. 2017 Oct 11;8(1):864.

Published In

Nat Commun

DOI

10.1038/s41467-017-00910-z

EISSN

2041-1723

Publication Date

October 11, 2017

Volume

8

Issue

1

Start / End Page

864

Location

England

Related Subject Headings

  • Obesity
  • Neoplasm Metastasis
  • Myeloid Cells
  • Mice, Inbred C57BL
  • Mice
  • Hydroxycholesterols
  • Humans
  • Female
  • Cholesterol, Dietary
  • Cell Line, Tumor