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HDL and LDL: Potential New Players in Breast Cancer Development

Discussion in 'Cardiology' started by Valery1957, Nov 8, 2019.

  1. Valery1957

    Valery1957 Well-Known Member

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    Journal of
    Clinical Medicine
    Review

    HDL and LDL: Potential New Players in Breast
    Cancer Development

    Lídia Cedó 1,2, Srinivasa T. Reddy 3, Eugènia Mato 1,5, Francisco Blanco-Vaca 1,2,4,* and
    Joan Carles Escolà-Gil 1,2,4,*
    1 Institut d’Investigacions Biomèdiques (IIB) Sant Pau, Sant Quintí 77, 08041 Barcelona, Spain;
    lcedo@santpau.cat (L.C.); emato@santpau.cat (E.M.)
    2 CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Monforte de Lemos 3-5,
    28029 Madrid, Spain
    3 Department of Molecular and Medical Pharmacology, David Geen School of Medicine,
    University of California, Los Angeles, CA 90095-1736, USA; sreddy@mednet.ucla.edu
    4 Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona,
    Av. de Can Domènech 737, 08193 Cerdanyola del Vallès, Spain
    5 CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Monforte de Lemos 3-5,
    28029 Madrid, Spain
    * Correspondence: fblancova@santpau.cat (F.B.-V.); jescola@santpau.cat (J.C.E.-G.);
    Tel.: +34-935537588 (F.B.-V. & J.C.E.-G.); Fax: +34-935537589 (F.B.-V. & J.C.E.-G.)
    Received: 29 May 2019; Accepted: 12 June 2019; Published: 14 June 2019
    Abstract: Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality
    in women. The identification of risk factors can improve prevention of cancer, and obesity and
    hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work,
    we review the progress to date in research on the potential role of the main cholesterol transporters,
    low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although
    some studies have failed to find associations between lipoproteins and breast cancer, some large clinical
    studies have demonstrated a direct association between LDL cholesterol levels and breast cancer
    risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast
    cancer cells and experimental mouse models of breast cancer have demonstrated an important role for
    cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol
    metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer
    cells and facilitates metastasis. Oxidative modification of the lipoproteins and HDL glycation activate
    dierent inflammation-related pathways, thereby enhancing cell proliferation and migration and
    inhibiting apoptosis. Cholesterol-lowering drugs and apolipoprotein A-I mimetics have emerged as
    potential therapeutic agents to prevent the deleterious eects of high cholesterol in breast cancer.
    Keywords: Breast cancer; cholesterol; 27-hydroxycholesterol; HDL; LDL; cholesterol-lowering therapies
    1. Introduction
    Breast cancer is the third most common cancer overall, with an estimated incidence of 1.7 million
    cases in 2016 and a 29% increase in incident cases between 2006 and 2016. Moreover, breast cancer
    was the fifth leading cause of cancer deaths for both sexes in 2016 and the primary cause of death for
    women [1]. A substantial proportion of the worldwide burden of cancer could be prevented; however,
    improved primary prevention of cancer requires identification of risk markers [2]. Reproductive,
    hormonal factors, and unhealthy lifestyles that trigger obesity are considered significant risk factors
    for breast cancer [3]. Obesity represents a potentially modifiable risk factor that could increase the risk
     

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