|Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis|
|Niu, Chenguang1,2,3,4; Pan, Bing1,2,3,4; Ren, Hui1,2,3,4; Lv, Xiaofeng5,6; Zhao, Yangyu7,8; Yu, Baoqi1,2,3,4; He, Yubin5,6; Ma, Yijing1,2,3,4; Kong, Jinge1,2,3,4; Yu, Fangzhu1,2,3,4; Sun, Wen-bing9; Zhang, Youyi1,2,3,4; Willard, Belinda10; Zheng, Lemin1,2,3,4|
|关键词||Breast Cancer Oxidative Stress Metastasis High-density Lipoprotein|
|刊名||JOURNAL OF TRANSLATIONAL MEDICINE|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, Research & Experimental|
|研究领域[WOS]||Research & Experimental Medicine|
|关键词[WOS]||HIGH-DENSITY-LIPOPROTEIN ; PROTEIN-KINASE-C ; ENDOTHELIAL-CELLS ; ADHESION MOLECULES ; SERUM-LIPIDS ; PKC-ALPHA ; CHOLESTEROL ; TARGET ; RISK ; ASSOCIATION|
Background: Previous 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.
Methods: Human 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.
Results: We found hypochlorite-oxidized HDL dramatically promotes breast cancer cell pulmonary metastasis (133.4% increase at P < 0.0 I 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 padinjection; 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 I for MDA-MB-231; 88.8% increase at P < 0.00 I for MCF7;), TC-HUVEC adhesion (43.4% increase at P < 0.00 I 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 I 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.
Conclusions: Our 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.
|项目编号||2010CB912504 ; 2011CB503900 ; 30900595 ; 30821001 ; 81172500 ; 81170101 ; 7102104 ; 7122106 ; 2009J01112 ; 20090001120039 ; 20100001120034|
|资助机构||"973" National ST Major Project ; National Natural Science Foundation of China ; Natural Science Foundation of Beijing ; Natural Science Foundation of Fujian ; State Education Ministry of China|
|作者单位||1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Inst Cardiovasc Sci, Beijing 100191, Peoples R China|
2.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Inst Syst Biomed, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Minist Hlth, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing 100191, Peoples R China
5.Mil Gen Hosp Beijing, Dept Cardiovasc Med, Beijing 100700, Peoples R China
6.Mil Gen Hosp Beijing, Dept Endocrinol, Beijing 100700, Peoples R China
7.Peking Univ, Dept Obstet & Gynecol, Hosp 3, Beijing 100191, Peoples R China
8.Peking Univ, Inst Vasc Med, Hosp 3, Beijing 100191, Peoples R China
9.Capital Med Univ, Beijing Chao Yang Hosp, Dept Hepatobiliary Surg, Beijing 100043, Peoples R China
10.Cleveland Clin, Prote Lab, Cleveland, OH 44195 USA
|Niu, Chenguang,Pan, Bing,Ren, Hui,et al. Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2012,10.|
|APA||Niu, Chenguang.,Pan, Bing.,Ren, Hui.,Lv, Xiaofeng.,Zhao, Yangyu.,...&Zheng, Lemin.(2012).Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis.JOURNAL OF TRANSLATIONAL MEDICINE,10.|
|MLA||Niu, Chenguang,et al."Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis".JOURNAL OF TRANSLATIONAL MEDICINE 10(2012).|
|art%3A10.1186%2F1479（3563KB）||期刊论文||作者接受稿||开放获取||CC BY-NC-SA||浏览 请求全文|