LIPOXYGENASE METABOLITES OF ARACHIDONIC AND LINOLEIC ACIDS MODULATE THE ADHESION OF TUMOR-CELLS TO ENDOTHELIUM VIA REGULATION OF PROTEIN-KINASE-C
LIPOXYGENASE METABOLITES OF ARACHIDONIC AND LINOLEIC ACIDS MODULATE THE ADHESION OF TUMOR-CELLS TO ENDOTHELIUM VIA REGULATION OF PROTEIN-KINASE-C
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DOI：
10.1091/mbc.2.12.1045
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发表时间：
1991-12-01
期刊：
影响因子：
--
通讯作者：
HONN, KV
中科院分区：
文献类型：
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作者：
LIU, B;TIMAR, J;HONN, KV
12(S)-羟基二十碳四烯酸(12[S]-HETE)和13(S)-羟基十八碳二烯酸(13[S]-HODE)分别是花生四烯酸和亚油酸的脂氧合酶代谢产物，已被认为在肿瘤转移过程中调节肿瘤细胞与内皮的黏附。大鼠Walker癌肉瘤(W256)细胞与大鼠内皮细胞单层的黏附在12(S)-HETE作用下被增强，而这种黏附作用被13(S)-HODE所阻断。蛋白激酶抑制剂、星形孢子素、钙磷蛋白C和1-(5-isoquinoline-sulfonyl)-2-methylpiperazine，可抑制12(S)-HETE增强W256细胞的黏附。佛波醇12-肉豆蔻酸酯-13-醋酸酯耗尽W256细胞蛋白激酶C(PKC)，使其丧失对12(S)-HETE的反应能力。12(S)-HETE处理W256细胞后，膜相关蛋白激酶C活性增加100%，而13(S)-HODE抑制12(S)-HETE对膜相关蛋白激酶C转位的影响。高效液相色谱分析表明，在W256细胞中，12-HETE和13-HODE分别是花生四烯酸和亚油酸的两种主要脂肪氧合酶代谢物。因此，这两种代谢产物可能为PKC的调控提供了另一条信号通路。此外，这些发现表明，12(S)-HETE和13(S)-HODE对肿瘤细胞与内皮细胞黏附的调节可能是一个依赖蛋白激酶C的过程。
12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE) and 13(S)-hydroxyoctadecadienoic acid (13[S]-HODE), lipoxygenase metabolites of arachidonic acid and linoleic acid, respectively, previously have been suggested to regulate tumor cell adhesion to endothelium during metastasis. Adhesion of rat Walker carcinosarcoma (W256) cells to a rat endothelial cell monolayer was enhanced after treatment with 12(S)-HETE and this 12(S)-HETE enhanced adhesion was blocked by 13(S)-HODE. Protein kinase inhibitors, staurosporine, calphostin C, and 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine, inhibited the 12(S)-HETE enhanced W256 cell adhesion. Depleting W256 cells of protein kinase C (PKC) with phorbol 12-myristate-13-acetate abolished their ability to respond to 12(S)-HETE. Treatment of W256 cells with 12(S)-HETE induced a 100% increase in membrane-associated PKC activity whereas 13(S)-HODE inhibited the effect of 12(S)-HETE on PKC translocation. High-performance liquid chromatographic analysis revealed that in W256 cells 12-HETE and 13-HODE were two of the major lipoxygenase metabilites of arachidonic acid and linoleic acid, respectively. Therefore, these two metabolites may provide an alternative signaling pathway for the regulation of PKC. Further, these findings suggest that the regulation of tumor cell adhesion to endothelium by 12(S)-HETE and 13(S)-HODE may be a PKC-dependent process.