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学科主题: 基础医学
题名:
HDL of Patients with Type 2 Diabetes Mellitus Elevates the Capability of Promoting Breast Cancer Metastasis
作者: Pan, Bing1,2; Ren, Hui1,2; He, Yubin3,4; Lv, Xiaofeng3,4; Ma, Yijing1,2; Li, Jing5; Huang, Li5; Yu, Baoqi1,2; Kong, Jian6; Niu, Chenguang1,2; Zhang, Youyi1,2; Sun, Wen-bing6; Zheng, Lemin1,2
刊名: CLINICAL CANCER RESEARCH
发表日期: 2012-03-01
DOI: 10.1158/1078-0432.CCR-11-0817
卷: 18, 期:5, 页:1246-1256
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: HIGH-DENSITY-LIPOPROTEIN ; SPHINGOSINE 1-PHOSPHATE RECEPTORS ; CORONARY HEART-DISEASE ; ENDOTHELIAL-CELLS ; ADHESION MOLECULES ; CARDIOVASCULAR-DISEASE ; CHOLESTEROL ; INFLAMMATION ; EXPRESSION ; PLASMA
英文摘要:

Purpose: Epidemiologic studies suggested complicated associations between type 2 diabetes mellitus and breast cancer. High-density lipoprotein (HDL) is inversely associated with the risk and mortality of breast cancer. Our study is to determine the different effects of normal and diabetic HDL on breast cancer cell metastasis.

Experimental Design: MDA-MB-231 and MCF7 cells were treated with N-HDL, D-HDL, G-HDL, and Ox-HDL. Cell metastasis potency was examined using a tail-vein injection model, and cell adhesion abilities to human umbilical vein endothelial cells (HUVEC) and extracellular matrix (ECM) were determined in vitro. Integrin expression and protein kinase C (PKC) activity were evaluated, and PKC inhibitor was applied.

Results: D-HDL dramatically promoted cell pulmonary metastasis (103.6% increase at P < 0.001 for MDA-MB-231 with 1 x 10(5) cell injection; 157.1% increase at P < 0.05 for MCF7 with 4 x 10(5) cell injection) and hepatic metastasis (18.1-fold increase at P < 0.001 for MCF7 with 4 x 10(5) cell injection), and stimulated higher TC-HUVECs adhesion (21.9% increase at P < 0.001 for MDA-MB-231; 23.6% increase at P < 0.05 for MCF7) and TC-ECM attachment (59.9% and 47.9% increase, respectively, for MDA-MB-231 and MCF7, both at P < 0.01) compared with N-HDL. D-HDL stimulated higher integrin (beta 1, beta 2, beta 3, and an) expression on cell surface and induced higher PKC activity. Increased TC-HUVECs and TC-ECM adhesion induced by D-HDL, G-HDL, and Ox-HDL could be inhibited by staurosporine.

Conclusions: Our study showed that glycation and oxidation of HDL in diabetic patients could lead to abnormal actions on breast cancer cell adhesion to HUVECs and ECM, thereby promoting metastasis progression of breast cancer. This will largely draw the attention of HDL-based treatments in the diabetes patients with breast cancer. Clin Cancer Res; 18(5); 1246-56. (C)2012 AACR.

语种: 英语
所属项目编号: 2010CB912504 ; 2011CB503900 ; 30900595 ; 30821001 ; 81172500 ; 81170101 ; 7102104 ; 7122106 ; 2009J01112 ; 70103-007 ; 20090001120039 ; 20100001120034
项目资助者: "973" National ST Major Project ; National Natural Science Foundation of China ; Natural Science Foundation of Beijing ; Natural Science Foundation of Fujian ; Peking University Health Science Center ; The Returned Overseas Chinese Scholars ; New Century Excellent Talents in Universities ; State Education Ministry of China
WOS记录号: WOS:000301040700009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67770
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Mil Gen Hosp Beijing, Dept Endocrinol, Beijing, Peoples R China
2.Mil Gen Hosp Beijing, Dept Cardiovasc Med, Beijing, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China
5.China Japan Friendship Hosp, Dept Cardiovasc Med, Beijing, Peoples R China
6.Capital Med Univ, Dept Hepatobiliary Surg, Beijing Chao Yang Hosp Affiliated, Beijing, Peoples R China

Recommended Citation:
Pan, Bing,Ren, Hui,He, Yubin,et al. HDL of Patients with Type 2 Diabetes Mellitus Elevates the Capability of Promoting Breast Cancer Metastasis[J]. CLINICAL CANCER RESEARCH,2012,18(5):1246-1256.
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