Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis

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.

Oxidized High-Density Lipoprotein Induces the Proliferation and Migration of Vascular Smooth Muscle Cells by Promoting the Production of ROS

“…The proproliferative and promigratory effects of ox-HDL were found to be positively correlated with intracellular NADPH oxidase activation and ROS production. enhances the proliferation, migration and invasion of breast cancer cells, while hypochlorite-induced oxidative stress elevates the capability of HDL to promote breast cancer metastasis, which demonstrates that ox-HDL and oxidative stress play essential roles in the proliferation and migration of cells 28,29) . In this study, our results showed that compared with N-HDL, ox-HDL significantly promoted the proliferation of VSMCs in a dose-dependent manner (Fig.…”

“…Synthetic phenotypes of VSMCs proliferate and migrate from the medial layer of the vessel migration and invasion of breast cancer cells, thereby promoting the progression of breast cancer 28) . Furthermore, hypochlorite-induced oxidative stress elevates the ability of HDL to promote breast cancer metastasis 29) . Meanwhile, oxidized HDL is dysfunctional in promoting endothelial repair both in vitro and in the reendothelialization of injured carotid arteries 30) .…”

Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging

“…Comparative analysis of SR-B1 expression in breast tissues revealed a high expression of SR-B1 in breast tumors compared to the healthy surrounding tissue (Cao et al, 2004; Shahzad et al, 2011). Additionally, reports from multiple studies, conducted with several cancer cells revealed that HDL can enhance their capacity for proliferation and migration (Gospodarowicz et al, 1982; Jozan et al, 1985; Rotheneder and Kostner, 1989; Pussinen et al, 2000; Pan et al, 2012a,b). Studies conducted by Danilo et al (2013) in MDA-MB-231 (triple negative breast cancer cells) have shown that pharmacological inhibition of SR-B1 (through BLT-1) or knockdown of SR-B1 resulted in a reduction in cell proliferation perhaps via a decreased activation of the Akt signaling pathway.…”

High‐density lipoprotein functionality and breast cancer: A potential therapeutic target

“…8 The HDL particles' composition, size, and structure could be altered under various circumstances, such as inflammation, aging, and diseases (HIV, psoriasis, and so forth). 10 In the current study, we have reviewed the recent evidence in relation to the role of HDL and its association with breast cancer, and the utility of methods for assessing HDL function as a potential measure of disease risk. 9 There is emerging data showing that high levels of HDL-C are associated with a lower risk of breast cancer.…”