Sphingosine 1-phosphate receptor expression profile in human gastric cancer cells: Differential regulation on the migration and proliferation
Sphingosine 1-phosphate receptor expression profile in human gastric cancer cells: Differential regulation on the migration and proliferation
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DOI：
10.1016/j.jss.2005.08.004
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发表时间：
2006-01-01
影响因子：
2.2
通讯作者：
Nagawa, H
中科院分区：
文献类型：
--
作者：
Yamashita, H;Kitayama, J;Nagawa, H
导论.鞘氨醇1-磷酸（S1 P）是一种生物活性溶血磷脂，来源于活化的血小板，已知其通过多种细胞类型上的至少5种G蛋白偶联受体诱导多种细胞反应。胃癌患者血小板和凝血功能异常是常见的。然而，这种血小板衍生的介质S1 P的作用和S1 P受体在胃癌细胞上的分布都没有完全了解。本研究的目的是探讨S1 P及其受体在胃癌发生发展中的可能作用。本研究采用改良Boyden小室法和MTS法检测了9株人胃癌细胞系中S1 P受体的表达，并分析了S1 P及其受体表达对细胞迁移和细胞增殖的影响。北方印迹分析显示，S1 P2在所有胃癌细胞系中均有不同程度的表达，S1 P3在4种胃癌细胞系中均有表达。S1 P1表达较弱，S1 P4或S1 P5均未检测到显著表达。加入S1 P可显著刺激主要表达S1 P3的MKN 1和HCG-27的迁移，这种作用可被百日咳毒素或渥曼青霉素有效抑制。相反，S1 P显著抑制仅表达S1 P2的AZ-521的迁移。这表明S1 P2和S1 P3介导的信号之间的平衡可能是决定胃癌细胞对S1 P的转移反应的关键。S1 P对所有三种细胞系都产生了微弱但显著的抗增殖作用，尽管这种作用并不显著。在这些细胞中，S1 P诱导细胞外信号调节激酶（ERK）磷酸化，同时伴有Akt的瞬时去磷酸化，这可能导致对细胞增殖的微弱影响。我们的研究结果表明，S1 P受体的表达可能决定了胃癌的生物学行为，因此针对每个S1 P受体的治疗干预可能在临床上有效地预防胃癌转移。(c)2006年爱思唯尔公司All rights reserved.
Introduction. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid, derived from activated platelet, that is known to induce diverse cellular responses through at least five G-protein-coupled receptors on various cell types. Abnormal platelet and coagulation activation is often seen in patients with gastric cancer. However, neither the effects of this platelet-derived mediator S1P nor the distribution of S1P receptors on the gastric cancer cell are fully understood. The aim of this study was to examine the possible role of S1P and its receptors in the progression of gastric cancer.Materials and methods. We characterized the expression profiles of S1P receptors in nine human gastric cancer cell lines and evaluated the relationship between the responses to S1P and its receptor expression on cell migration by modified Boyden chamber and cell proliferation by MTS assay.Results. Northern blotting analysis has revealed that S1P2 was expressed in all gastric cancer cell lines to varying degrees, and S1P3 was expressed in four cell lines. S1P1 expression was weak, and no significant expression of either S1P4 or S1P5 was detected. The addition of S1P markedly stimulated the migration of MKN1 and HCG-27 that dominantly expressed S1P3, and the effect was potently inhibited by pertussis toxin or wortmannin. In contrast, S1P significantly inhibited the migration of AZ-521 that expressed S1P2 exclusively. This indicates that the balance between S1P2- and S1P3-mediated signals might be critical in determining the metastatic response of gastric cancer cells to S1P. S1P elicited weak but significant antiproliferative effects on all of the three cell lines, although the effects were not major. In these cells, S1P induced extracellular signal-regulated kinase (ERK) phosphorylation with transient Akt dephosphorylation that may cause the weak effects on proliferation.Conclusions. Our results suggest that the S1P receptor expression may critically determine the biological behavior of gastric cancers and thus therapeutic interventions directed at each S1P receptor might be clinically effective in preventing metastasis in gastric cancer. (c) 2006 Elsevier Inc. All rights reserved.