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

Autor: Yangyu Zhao, Belinda Willard, Xiaofeng Lv, Yijing Ma, Hui Ren, Wen bing Sun, Jinge Kong, Chenguang Niu, Lemin Zheng, Fangzhu Yu, Baoqi Yu, Bing Pan, Youyi Zhang, Yubin He
Jazyk: angličtina
Předmět:
Integrins
Lung Neoplasms
Cell
lcsh:Medicine
medicine.disease_cause
Metastasis
Extracellular matrix
Mice
chemistry.chemical_compound
Breast cancer
High-density lipoprotein
Cell Movement
Neoplasm Metastasis
RNA
Small Interfering
skin and connective tissue diseases
Protein Kinase C
Medicine(all)
Mice
Inbred BALB C
Liver Neoplasms
General Medicine
Extracellular Matrix
medicine.anatomical_structure
Female
Lipoproteins
HDL
Biology
General Biochemistry
Genetics and Molecular Biology
Cell Line
Tumor
Cell Adhesion
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Neoplasm Invasiveness
Gene Silencing
Cell adhesion
Protein Kinase Inhibitors
Cell Proliferation
Cell growth
Biochemistry
Genetics and Molecular Biology(all)
Research
lcsh:R
Mammary Neoplasms
Experimental
medicine.disease
Xenograft Model Antitumor Assays
Hypochlorous Acid
chemistry
Oxidative stress
Cancer research
Zdroj: Journal of Translational Medicine, Vol 10, Iss 1, p 65 (2012)
Journal of Translational Medicine
ISSN: 1479-5876
DOI: 10.1186/1479-5876-10-65
Popis: 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.
Databáze: OpenAIRE
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