Sphingosine 1-phosphate receptor expression profile and regulation of migration in human thyroid cancer cells
Sphingosine 1-phosphate receptor expression profile and regulation of migration in human thyroid cancer cells
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DOI：
10.1042/bj20060299
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发表时间：
2006-09-15
影响因子：
4.1
通讯作者：
Tornquist, Kid
中科院分区：
文献类型：
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作者：
Balthasar, Sonja;Samulin, Johanna;Tornquist, Kid
在1株乳头状（NPA）、2株滤泡状（ML-1、WRO）和2株间变性（FRO、ARO）甲状腺癌细胞以及原代培养的人甲状腺细胞中，研究了S1P（鞘氨醇i -磷酸）受体的表达及其对迁移的影响。此外，我们还研究了SIP对ML-1和FRO细胞增殖、粘附和钙信号传导的影响。所有细胞类型均表达多个S1P受体。在原代培养、ML-1细胞和FRO细胞中，SIP可诱发细胞内钙信号。原代培养不影响增殖和迁移，而S1P部分抑制ML-1和FRO细胞的增殖。低纳摩尔浓度的SIP抑制了FRO、WRO和ARO细胞的迁移，但刺激了ML-1细胞的迁移。与此一致的是，介导迁移反应的S1P(1)和S1P(3)在ML-1细胞中强烈表达，而抑制迁移的S1P(2)在其他细胞系中占主导地位。ML-1细胞的迁移作用是由G(i)和磷脂酰肌醇3-激酶介导的。SIP和S1P(1)特异性激动剂SEW-2871均诱导Akt在Ser（473）位点磷酸化。然而，SEW-2871不能刺激迁移，而S1P(1)/S1P(3)拮抗剂VPC 23019抑制sip诱导的迁移。结果表明，异常的S1P受体表达可能会促进甲状腺癌细胞的迁移，从而促进某些甲状腺肿瘤的转移行为。
S1P(sphingosine I-phosphate) receptor expression and the effects of S1P on migration were studied in one papillary (NPA), two follicular (ML-1, WRO) and two anaplastic (FRO, ARO) thyroid cancer cell lines, as well as in human thyroid cells in primary culture. Additionally, the effects of SIP on proliferation, adhesion and calcium signalling were addressed in ML-1 and FRO cells. All cell types expressed multiple S1P receptors. SIP evoked intracellular calcium signalling in primary cultures, ML-1 cells and FRO cells. Neither proliferation nor migration was affected in primary cultures, whereas S1P partly inhibited proliferation in ML-1 and FRO cells. Low nanomolar concentrations of SIP inhibited migration in FRO, WRO and ARO cells, but stimulated ML-1 cell migration. Consistently, S1P(1) and S1P(3), which mediate migratory responses, were strongly expressed in ML-1 cells, and S1P(2), which inhibits migration, was the dominating receptor in the other cell lines. The migratory effect in ML-1 cells was mediated by G(i) and phosphatidylinositol 3-kinase. Both SIP and the S1P(1)-specific agonist SEW-2871 induced Akt phosphorylation at Ser(473). However, SEW-2871 failed to stimulate migration, whereas the S1P(1)/S1P(3) antagonist VPC 23019 inhibited SIP-induced migration. The results suggest that aberrant S1P receptor expression may enhance thyroid cancer cell migration and thus contribute to the metastatic behaviour of some thyroid tumours.