Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study.

David De Gonzalo-Calvo,Agusti Barnadas,Daniel Escuin,Maitane Perez-Olabarria,Laura López-Vilaró,Enrique Lerma,Laura Nasarre,Lina Badimon,Vicenta Llorente-Cortés,Tania Vázquez

doi:10.1186/s12885-015-1469-5

David De Gonzalo-Calvo, Agusti Barnadas + Show 8 more

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https://doi.org/10.1186/s12885-015-1469-5

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Abstract

BackgroundThe metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood. The objective was to analyze the relationship between intratumor CE content and clinicopathological variables in human breast carcinomas.MethodsWe classified 30 breast carcinoma samples into three subgroups: 10 luminal-A tumors (ER+/PR+/Her2-), 10 Her-2 tumors (ER-/PR-/Her2+), and 10 triple negative (TN) tumors (ER-/PR-/Her2-). We analyzed intratumor neutral CE, free cholesterol (FC) and triglyceride (TG) content by thin layer chromatography after lipid extraction. RNA and protein levels of lipid metabolism and invasion mediators were analyzed by real time PCR and Western blot analysis.ResultsGroup-wise comparisons, linear regression and logistic regression models showed a close association between CE-rich tumors and higher histologic grade, Ki-67 and tumor necrosis. CE-rich tumors displayed higher mRNA and protein levels of low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SCARB1). An increased expression of acetyl-Coenzyme A acetyltransferase 1 (ACAT1) in CE-rich tumors was also reported.ConclusionsIntratumor CE accumulation is intimately linked to proliferation and aggressive potential of breast cancer tumors. Our data support the link between intratumor CE content and poor clinical outcome and open the door to new antitumor interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1469-5) contains supplementary material, which is available to authorized users.

Highlights

The metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood
We found that mechanisms potentially involved in intratumoral CE accumulation may be lipid internalization through the overexpression of low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SCARB1) receptors and cholesterol esterification through the upregulation of ACAT1 enzyme
Results for the present study showed a tight correlation between intratumor CE accumulation and LDLR expression and that both LDLR mRNA and protein levels were significantly elevated in CE-rich breast carcinomas

Summary

Introduction

The metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood. Plasma lipoproteins are a source of fatty acids (FA) and cholesteryl esters (CE) for tumor cells. Availability of intratumoral CE reduces de Gonzalo-Calvo et al BMC Cancer (2015) 15:460 de novo lipid synthesis, favors membrane biogenesis, induces lipid raft formation and alters tumor cell signaling, essential processes for tumor proliferation, invasiveness and survival [18,19,20]. In concordance with these data, the inhibition of CE synthesis has anticancer effects [21, 22]

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