Abstract

Although there are many subtypes of breast cancer, inflammatory breast cancer (IBC) is arguably the deadliest. Research over the past decade has demonstrated that IBC is a distinct entity from other forms of breast cancer. Important risk factors that have been associated with the development of aggressive breast cancers, such as IBC, include obesity and diet, which are evident in the United States, where the overconsumption of high-fat foods continues to contribute to obesity in the nation. Here we investigate differences in cholesterol uptake and storage between IBC, non-IBC, and mammary epithelial cell lines. Our results demonstrate that compared with human mammary epithelial cells (HMECs), both IBC and non-IBC cells have increased cholesterol content. IBC cells retain intracellular cholesterol esters, free cholesterol, and triglycerides in lipid-deficient environments. In contrast, we observe in cell-type-of-origin-matched non-IBC a significant decrease in lipid content under the same lipid-deficient conditions. These data suggest that cholesterol storage may be affected by the cholesterol content of the environment where the tumor cell was isolated. Here, we suggest that breast cancer cells may migrate when they are unable to obtain cholesterol from their extracellular environments.

Highlights

  • Breast cancer affects approximately 1 in 8 women making it the most commonly occurring cancer in women in the United States [1]

  • The results of the Fetal bovine serum Lipoprotein Deficient Serum (LPDS) (FBS) control Oil Red O (ORO) staining suggest that the malignant cell lines initially contain a significantly larger amount of neutral lipid droplets, containing cholesterol, cholesterol esters, and triglycerides, than the noncancerous cell line

  • Since we observed similar increases in mRNA expression of the Low-Density Lipoprotein (LDL)-R in the Inflammatory Breast Cancer (IBC) and human mammary epithelial cell (HMEC), but not the nonIBC cells grown in LPDS, we focused on LDL-R protein expression

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Summary

Introduction

Breast cancer affects approximately 1 in 8 women making it the most commonly occurring cancer in women in the United States [1]. The highly aggressive and metastatic nature of IBC contributes to the low 3-year disease-free survival rate of less than 40%, as compared to approximately 90% for nonIBCs [5]. Differences in expression of molecules associated with progression such as E-cadherin or caveolins have opposite trends in IBC versus non-IBC (reviewed in [8]). These differences present significant challenges in treating this aggressive disease with traditional breast cancer therapies. In order to identify innovative and effective treatment plans for both IBC and non-IBCs it is important to further our understanding of cellular characteristics that distinguish the two diseases from each other

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