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Abstract PR3: The cholesterol metabolite 27-hydroxycholesterol increases breast cancer tumor growth and metastasis

Publication ,  Journal Article
Nelson, ER; Wardell, SE; Howe, MK; Carver, NJ; Umetani, M; McDonnell, DP
Published in: Cancer Research
February 1, 2013

Breast cancer remains the most common cancer and is the second leading cause of cancer death in women. The magnitude of this problem provides strong rationale for studies that may lead to the development of new chemopreventative strategies and/or lifestyle changes that reduce cancer incidence. It is of significance, therefore, that circulating cholesterol has been correlated to the development of breast cancer, and patients taking lipophilic inhibitors of 2-hydroxy-3-methylglutaryl coenzyme A (statins) demonstrate significantly lower breast cancer incidence, and decreased breast cancer recurrence. Therefore, our recent finding that 27-Hydroxycholesterol (27HC), a primary metabolite of cholesterol, exerts partial agonist activity on both the estrogen receptors (ERs) and liver X receptors (LXRs) suggests a potential, mechanistic link between hypercholesterolemia and breast cancer incidence. Importantly, the enzyme responsible for the conversion of cholesterol to 27HC (CYP27A1) is primarily expressed in macrophages, and it is well established that tumor infiltrating macrophages are associated with more aggressive tumors and worse patient outcome. Therefore, we initiated a series of studies to determine the impact of 27HC on breast cancer pathophysiology. Here, we demonstrate that (1) macrophage produced 27HC increases breast cancer cell proliferation, (2) elevation of exogenous 27HC increases in vivo tumor growth and lung metastases, and (3) genetic ablation of the enzyme responsible for 27HC synthesis increases latency, and reduces tumor growth and metastasis. Our ongoing work is aimed at identifying the mechanisms responsible for the 27HC induced increase in metastasis. In summary, our data thus far strongly indicate a role for macrophage produced 27HC in breast cancer pathophysiology and metastasis. The results provide additional support for the exploration of potential chemopreventative benefits of lower cholesterol diets, pharmacological inhibitors of HMG-CoA reductase or CYP27A1, and macrophage ablative strategies.DOD Postdoctoral Award BC085585 (ERN), NIH 5R37DK048807 (DPM).This abstract is also presented as Poster B50.Citation Format: Erik Russell Nelson, Suzanne E. Wardell, Matthew K. Howe, Nicole J. Carver, Michihisa Umetani, Donald P. McDonnell. The cholesterol metabolite 27-hydroxycholesterol increases breast cancer tumor growth and metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr PR3.

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

February 1, 2013

Volume

73

Issue

3_Supplement

Start / End Page

PR3 / PR3

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nelson, E. R., Wardell, S. E., Howe, M. K., Carver, N. J., Umetani, M., & McDonnell, D. P. (2013). Abstract PR3: The cholesterol metabolite 27-hydroxycholesterol increases breast cancer tumor growth and metastasis. Cancer Research, 73(3_Supplement), PR3–PR3. https://doi.org/10.1158/1538-7445.tim2013-pr3
Nelson, Erik Russell, Suzanne E. Wardell, Matthew K. Howe, Nicole J. Carver, Michihisa Umetani, and Donald P. McDonnell. “Abstract PR3: The cholesterol metabolite 27-hydroxycholesterol increases breast cancer tumor growth and metastasis.” Cancer Research 73, no. 3_Supplement (February 1, 2013): PR3–PR3. https://doi.org/10.1158/1538-7445.tim2013-pr3.
Nelson ER, Wardell SE, Howe MK, Carver NJ, Umetani M, McDonnell DP. Abstract PR3: The cholesterol metabolite 27-hydroxycholesterol increases breast cancer tumor growth and metastasis. Cancer Research. 2013 Feb 1;73(3_Supplement):PR3–PR3.
Nelson, Erik Russell, et al. “Abstract PR3: The cholesterol metabolite 27-hydroxycholesterol increases breast cancer tumor growth and metastasis.” Cancer Research, vol. 73, no. 3_Supplement, American Association for Cancer Research (AACR), Feb. 2013, pp. PR3–PR3. Crossref, doi:10.1158/1538-7445.tim2013-pr3.
Nelson ER, Wardell SE, Howe MK, Carver NJ, Umetani M, McDonnell DP. Abstract PR3: The cholesterol metabolite 27-hydroxycholesterol increases breast cancer tumor growth and metastasis. Cancer Research. American Association for Cancer Research (AACR); 2013 Feb 1;73(3_Supplement):PR3–PR3.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

February 1, 2013

Volume

73

Issue

3_Supplement

Start / End Page

PR3 / PR3

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis