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Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Translational Medicine

, 10:65

First Online: 30 March 2012Received: 19 December 2011Accepted: 30 March 2012DOI: 10.1186-1479-5876-10-65

Cite this article as: Pan, B., Ren, H., Lv, X. et al. J Transl Med 2012 10: 65. doi:10.1186-1479-5876-10-65

Abstract

BackgroundPrevious studies suggest that oxidative stress plays an important role in the development of breast cancer. There is a significant inverse relationship between HDL and the risk and mortality of breast cancer. However, it is well known that under conditions of oxidative stress, such as breast cancer, HDL can be oxidatively modifiedand these modifications may have an effect on the functions of HDL. The purpose of this study is to determine the different effects of normal and oxidized caused by hypochlorite-induced oxidative stress HDL on breast cancer cell metastasis.

MethodsHuman breast cancer cell lines were treated with normal and hypochlorite-oxidized HDL, and then cell metastasis potency in vivo and the abilities of migration, invasion, adhesion to HUVEC and ECM in vitro were examined. Integrin expression and PKC activity were evaluated, and PKC inhibitor and PKC siRNA was applied.

ResultsWe found hypochlorite-oxidized HDL dramatically promotes breast cancer cell pulmonary metastasis 133.4% increase at P < 0.0 l for MDA-MB-231 by mammary fat pad injection; 164.3% increase at P < 0.01 for MCF7 by tail vein injection and hepatic metastasis 420% increase at P < 0.0 l for MDA-MB-231 by mammary fat pad injection; 1840% fold increase at P < 0.001 for MCF7 by tail vein injection in nude mice, and stimulates higher cell invasion 85.1% increase at P < 0.00 l for MDA-MB-231; 88.8% increase at P < 0.00 l for MCF7;, TC-HUVEC adhesion 43.4% increase at P < 0.00 l for MDA-MB-231; 35.2% increase at P < 0.00 l for MCF7, and TC-ECM attachment 41.0% increase at P < 0.00 l for MDA-MB-231; 26.7% increase at P < 0.05 for MCF7 in vitro compared with normal HDL. The data also shows that the PKC pathway is involved in the abnormal actions of hypochlorite-oxidized HDL.

ConclusionsOur study demonstrated that HDL under hypochlorite-induced oxidative stress stimulates breast cancer cell migration, invasion, adhesion to HUVEC and ECM, thereby promoting metastasis of breast cancer. These results suggest that HDL-based treatments should be considered for treatment of breast cancer patients.

KeywordsBreast cancer Oxidative stress Metastasis High-density lipoprotein AbbreviationsHDLhigh-density lipoprotein

LDLlow-density lipoprotein

apoA-Iapolipoprotein A-I

TCtumor cells

HUVEChuman umbilical vein endothelial cells

ECMextracellular matrix

PKCprotein kinase C

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-10-65 contains supplementary material, which is available to authorized users.

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Autor: Bing Pan - Hui Ren - Xiaofeng Lv - Yangyu Zhao - Baoqi Yu - Yubin He - Yijing Ma - Chenguang Niu - Jinge Kong - Fangzhu 

Fuente: https://link.springer.com/







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