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学科主题: 基础医学
题名:
Role of Vimentin in the Inhibitory Effects of Low-Molecular-Weight Heparin on PC-3M Cell Adhesion to, and Migration through, Endothelium
作者: Pan, Yan; Lei, Tianluo; Teng, Bao; Liu, Jihong; Zhang, Jianzhao; An, Yu; Xiao, Yuan; Han, Jing; Pan, Xueyang; Wang, Junhua; Yu, Heming; Ren, Hong; Li, Xuejun1
刊名: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
发表日期: 2011-10-01
DOI: 10.1124/jpet.111.182055
卷: 339, 期:1, 页:82-92
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: IN-VITRO ; TRANSENDOTHELIAL MIGRATION ; CYTOSOLIC CALCIUM ; BREAST-CANCER ; TUMOR-CELLS ; EXPRESSION ; CYTOSKELETON ; CONTACT ; MATRIX ; PERMEABILITY
英文摘要:

Low-molecular-weight heparin (LMWH) has been used in cancer patients with venous thromboembolic complications, resulting in a higher survival rate and an inhibitory action on experimental metastasis. In the present study, human umbilical vein endothelial cells (HUVECs) were treated with LMWH for 24 h. We found that the resulting HUVECs could significantly inhibit the highly metastatic human prostate cancer cell line (PC-3M) in terms of its adhesion to the endothelium and migration across the endothelium, according to scanning electron microscopy. We also determined the elevated levels of endothelial intercellular Ca2+ concentration after the adhesion of PC-3M cells to HUVECs was greatly reduced by incubation with LMWH. Using proteomics, we surveyed the global protein changes in HUVECs after LMWH treatment and identified four down-regulated proteins that were possible isoforms of cytoskeletal vimentin intermediate filaments, cartilage-derived C-type lectin, and serine/threonine protein phosphatase 1 beta (PP-1B). LMWH affected the morphology of vimentin and the expression levels of alpha(v) integrin and PP-1B in HUVECs bound to PC-3M cells. Vimentin assists in the adhesion of PC-3M cells, which was confirmed by short interfering RNA experiments. Furthermore, the direct binding of purified vimentin protein with LMWH was detected with surface plasmon resonance methods. However, when we used fluorescence-labeled heparin for 24 h to identify whether this binding occurred within cells, heparin was distributed principally around endothelial cells. Taken together, these findings suggest that the monoincubation of LMWH with HUVECs could inhibit PC-3M cell adhesion to, and migration through, endothelium. LMWH′s regulation of vimentin plays a role in the antimetastatic action.

语种: 英语
所属项目编号: 81020108031 ; 30572202 ; 30973558 ; 30772571 ; 30901803 ; 30901815 ; 2009ZX09103-144 ; B07001
项目资助者: National Natural Science Foundation of China ; Ministry of Science and Technology in China ; Ministry of Education of China ; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China
WOS记录号: WOS:000294998900009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58523
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Peking Univ, Inst Syst Biomed, Beijing 100191, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Pharmacol, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Pan, Yan,Lei, Tianluo,Teng, Bao,et al. Role of Vimentin in the Inhibitory Effects of Low-Molecular-Weight Heparin on PC-3M Cell Adhesion to, and Migration through, Endothelium[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,2011,339(1):82-92.
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