Apolipoprotein-mediated regulation of lipid metabolism induces distinctive effects in different types of breast cancer cells

Céline Ben Hassen,Gaëlle Fromont,Roseline Guibon,Philippe G Frank,Jorge L Gutierrez-Pajares,Michelle Pinault,Cyrille Guimaraes

doi:10.1186/s13058-020-01276-9

Céline Ben Hassen, Gaëlle Fromont + Show 5 more

Open Access

https://doi.org/10.1186/s13058-020-01276-9

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Abstract

BackgroundThe highest incidence of breast cancer is in the Western world. Several aspects of the Western lifestyle are known risk factors for breast cancer. In particular, previous studies have shown that cholesterol levels can play an important role in the regulation of tumor progression.MethodsIn the present study, we modulated cholesterol metabolism in the human breast cancer cell lines MCF-7 and MDA-MB-231 using a genetic approach. Apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE) were expressed in these cell lines to modulate cholesterol metabolism. The effects of these apolipoproteins on cancer cell properties were examined.ResultsOur results show that both apolipoproteins can regulate cholesterol metabolism and can control the epithelial-to-mesenchymal transition process. However, these effects were different depending on the cell type. We show that expressing apoA-I or apoE stimulates proliferation, migration, and tumor growth of MCF-7 cells. However, apoA-I or apoE reduces proliferation and migration of MDA-MB-231 cells.ConclusionsThese data suggest that modulating sterol metabolism may be most effective at limiting tumor progression in models of triple-negative cancers.

Highlights

The highest incidence of breast cancer is in the Western world
ApoA-I and ApoE expression regulate cellular cholesterol distribution in MCF-7 and MDA-MB-231 Results presented in Fig. 1 are based upon the data generated by the TCGA Research Network [20]
Determination of cellular membrane fluidity changes Since the cholesterol content of biological membranes is an important regulator of membrane fluidity [25], we examined whether apolipoprotein expression could affect membrane fluidity in the different cell lines

Summary

Introduction

The highest incidence of breast cancer is in the Western world. Several aspects of Western lifestyles are known risk factors for breast cancer. Diets high in saturated fat, early menarche, low parity, and advanced age at first pregnancy are established risk factors for breast cancer [1]. All of these risks are more common in Western countries. Only 10% of breast cancer cases have a genetic origin [1]. In the Western world, environmental factors appear to have a. The highest incidence of breast cancer is in the Western world. Several aspects of the Western lifestyle are known risk factors for breast cancer. Previous studies have shown that cholesterol levels can play an important role in the regulation of tumor progression

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Results

Discussion

Conclusion