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

Abstract

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 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.

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.

• Authors: Bing Pan, Hui Ren, Xiaofeng Lv, Yangyu Zhao, Baoqi Yu, Yubin He, Yijing Ma, Chenguang Niu, Jinge Kong, Fangzhu Yu, Wen-bing Sun, Youyi Zhang, Belinda Willard, Lemin Zheng
• Journal: Journal of translational medicine (J Transl Med) Vol. 10 Pg. 65 (Mar 30 2012) ISSN: 1479-5876 [Electronic] England
• PMID: 22462581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Integrins
• Lipoproteins, HDL
• Protein Kinase Inhibitors
• RNA, Small Interfering
• Hypochlorous Acid
• Protein Kinase C

Topics

• Animals
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Extracellular Matrix (drug effects, metabolism)
• Female
• Gene Silencing (drug effects)
• Human Umbilical Vein Endothelial Cells
• Humans
• Hypochlorous Acid (toxicity)
• Integrins (metabolism)
• Lipoproteins, HDL (metabolism)
• Liver Neoplasms (pathology, secondary)
• Lung Neoplasms (pathology, secondary)
• Mammary Neoplasms, Experimental (metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Oxidative Stress (drug effects)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• RNA, Small Interfering (metabolism)
• Xenograft Model Antitumor Assays