Hypercholesterolemia induces angiogenesis and accelerates growth of breast tumors in vivo.

Am J Pathol

The Program in Vascular Biology, Boston Children's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts.

Published: July 2014

AI Article Synopsis

  • Obesity and metabolic syndrome in postmenopausal women are linked to higher breast cancer rates, often associated with high cholesterol levels.
  • Experimental studies on mice showed that mice fed a high-fat/high-cholesterol diet had faster tumor progression and higher microvessel density than those on lower cholesterol diets.
  • The research indicates that high cholesterol significantly promotes tumor growth by increasing cell proliferation and reducing apoptosis, suggesting that managing cholesterol levels may be crucial in breast cancer progression.

Article Abstract

Obesity and metabolic syndrome are linked to an increased prevalence of breast cancer among postmenopausal women. A common feature of obesity, metabolic syndrome, and a Western diet rich in saturated fat is a high level of circulating cholesterol. Epidemiological reports investigating the relationship between high circulating cholesterol levels, cholesterol-lowering drugs, and breast cancer are conflicting. Here, we modeled this complex condition in a well-controlled, preclinical animal model using innovative isocaloric diets. Female severe combined immunodeficient mice were fed a low-fat/no-cholesterol diet and then randomized to four isocaloric diet groups: low-fat/no-cholesterol diet, with or without ezetimibe (cholesterol-lowering drug), and high-fat/high-cholesterol diet, with or without ezetimibe. Mice were implanted orthotopically with MDA-MB-231 cells. Breast tumors from animals fed the high-fat/high-cholesterol diet exhibited the fastest progression. Significant differences in serum cholesterol level between groups were achieved and maintained throughout the study; however, no differences were observed in intratumoral cholesterol levels. To determine the mechanism of cholesterol-induced tumor progression, we analyzed tumor proliferation, apoptosis, and angiogenesis and found a significantly greater percentage of proliferating cells from mice fed the high-fat/high-cholesterol diet. Tumors from hypercholesterolemic animals displayed significantly less apoptosis compared with the other groups. Tumors from high-fat/high-cholesterol mice had significantly higher microvessel density compared with tumors from the other groups. These results demonstrate that hypercholesterolemia induces angiogenesis and accelerates breast tumor growth in vivo.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076468PMC
http://dx.doi.org/10.1016/j.ajpath.2014.03.006DOI Listing

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