12(S)‐hete promotes tumor‐cell adhesion by increasing surface expression of αVβ3 integrins on endothelial cells

12(S)‐hete promotes tumor‐cell adhesion by increasing surface expression of αVβ3 integrins on endothelial cells
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12(S)-hete 通过增加内皮细胞上 αVβ3 整合素的表面表达来促进肿瘤细胞粘附

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发表时间:
1993
期刊:
影响因子:
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通讯作者:
K. Honn
K. Honn
中科院分区:
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文献类型:
--
作者:
D. Tang;I. Grossi;Yong Q. Chen;C. Diglio;K. Honn;K. Honn

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本研究旨在研究花生四烯酸脂氧合酶代谢产物12(S)-HETE对内皮细胞(大鼠主动脉内皮细胞,或RAEC)αvβ3整合素受体表面表达的调节作用。几种单克隆和多克隆抗体定位了融合后和融合后RAEC中的粘着斑中的αvβ3。RAEC αvβ3整合素进一步通过免疫印迹和免疫沉淀进行表征。12(S)-HETE(而非12(R)-HETE或其他脂氧合酶衍生的羟基脂肪酸)诱导RAEC中αvβ3表面表达的剂量依赖性增加,前列环素或其类似物伊洛前列素以及13-HODE(亚油酸的15-脂氧合酶产物)可拮抗该作用。12(S)-HETE促进RAEC与玻连蛋白的粘附,抗αvβ3抗体可抑制这种作用12(S)-HETE还促进肿瘤细胞(W256癌肉瘤)与玻连蛋白的粘附,抗αIIbβ3的各种抗体可抑制这种粘附,但抗αv β 3的抗体不抑制这种粘附。W256与12(S)-HETE-处理的RAEC的粘附表现出显著增加,抗-αv、-β3或-αvβ 3抗体和13-HODE可抑制该粘附。Western blotting、免疫沉淀和逆转录聚合酶链反应表明,W256癌肉瘤细胞表达αIIbβ3整合素,但不表达αvβ3。结果表明,脂氧合酶代谢物[即,12(S)-HETE和13-HODE]通过增强内皮细胞整联蛋白(例如,αvβ3)表达。
The present work was undertaken to investigate the regulatory role of 12(S)‐HETE, a lipoxygenase metabolite of arachidonic acid, in the surface expression of αvβ3 integrin receptors in endothelial cells (rat aortic endothelial cells, or RAEC). Several monoclonal and polyclonal antibodies localized αvβ3 in focal adhesions in both subconfluent and post‐confluent RAEC. RAEC αvβ3 integrins were further characterized by immunoblotting and immunoprecipitation. 12(S)‐HETE, but not 12(R)‐HETE or other lipoxygenase‐derived hydroxy fatty acids, induced a dose‐dependent increase in αvβ3 surface expression in RAEC, which was antagonized by prostacyclin or its analog iloprost as well as by 13‐HODE, a 15‐lipoxygenase product of linoleic acid. 12(S)‐HETE promoted RAEC adhesion to vitronectin, an effect inhibited by antibodies against αvβ3 12(S)‐HETE also promoted tumor‐cell (W256 carcinosarcoma) adhesion to vitronectin, which was inhibited by various antibodies against αIIbβ3 but not by an antibody against αv. W256 adhesion to 12(S)‐HETE‐treated RAEC demonstrated a significant increase, which was inhibited by anti‐αv, ‐β3, or ‐αvβ3antibodies and by 13‐HODE. Western blotting, immunoprecipitation and reverse transcription‐polymerase chain reaction indicated that W256 carcinosarcoma cells expressed αIIbβ3 integrins but not αvβ3. The results suggest that the lipoxygenase metabolites [i.e., 12(S)‐HETE and 13‐HODE] play a significant role in modulating tumor‐cell interactions with en'dothelium by enhancing endothelial cell integrin (e.g., αvβ3)expression.
配体桥接介导整合素 α IIb beta 3(血小板 GPIIB-IIIA)依赖性同型和异型细胞间相互作用。
DOI: 10.1172/jci115412
发表时间: 1991
期刊: The Journal of clinical investigation
影响因子: --
作者:
Gawaz,MP;Loftus,JC;Bajt,ML;Frojmovic,MM;Plow,EF;Ginsberg,MH
通讯作者: Ginsberg,MH
DOI: --
发表时间: 1989
期刊: The Journal of biological chemistry
影响因子: --
作者:
Ignotz,RA;Heino,J;Massagué,J
通讯作者: Massagué,J
通过花生四烯酸和亚油酸的脂氧合酶产物双向控制肿瘤细胞 IRGpIIb/IIIa 受体的膜表达和/或激活以及肿瘤细胞粘附。
DOI: --
发表时间: 1989
期刊: Cancer research
影响因子: 11.2
作者:
Grossi,IM;Fitzgerald,LA;Umbarger,LA;Nelson,KK;Diglio,CA;Taylor,JD;Honn,KV
通讯作者: Honn,KV
小鼠肿瘤细胞中 α IIb β 3 整合素的鉴定。
DOI: --
发表时间: 1992
期刊: The Journal of biological chemistry
影响因子: --
作者:
Chen,YQ;Gao,X;Timar,J;Tang,D;Grossi,IM;Chelladurai,M;Kunicki,TJ;Fligiel,SE;Taylor,JD;Honn,KV
通讯作者: Honn,KV
DOI: 10.1165/ajrcmb/4.3.195
发表时间: 1991-03-01
影响因子: 6.4
作者:
ALBELDA, SM
通讯作者: ALBELDA, SM