Phosphatidylinositol 3-kinase in the G protein-coupled receptor- induced chemokinesis and chemotaxis of MDA-MB-468 breast carcinoma cells: A comparison with leukocytes
Phosphatidylinositol 3-kinase in the G protein-coupled receptor- induced chemokinesis and chemotaxis of MDA-MB-468 breast carcinoma cells: A comparison with leukocytes
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DOI：
10.1158/1541-7786.mcr-06-0030
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发表时间：
2006-06-01
影响因子：
5.2
通讯作者：
Entschladen, Frank
中科院分区：
文献类型：
--
作者：
Bastian, Philipp;Posch, Birte;Entschladen, Frank
肿瘤细胞和白细胞分化为前端和后端是其自主定向运动的重要前提。磷脂酰肌醇3-激酶（PI3K）被认为在这一极化过程中起重要作用，然而不同细胞类型和不同迁移实验得到的结果差异很大。因此，我们以MDA-MB-468乳腺癌细胞为例，与ctl和中性粒细胞比较，对PI3K在肿瘤细胞运动活性和迁移方向性中的作用进行了比较研究。我们使用我们完善的、基于胶原蛋白的三维迁移实验来研究这些细胞的趋化作用和趋化性。我们的研究结果表明，PI3K在调节迁移活性中的作用在所研究的细胞类型之间是不同的：用wortmannin抑制PI3K会损害ctl和MDA-MB-468细胞的迁移，而中性粒细胞仅受到轻微影响。然而，两种细胞类型对G蛋白偶联受体配体梯度的化学反应能力均未受损。由此可见，PI3K参与调节MDA-MB-468乳腺癌细胞的迁移活性，而不参与其迁移的方向性。关于癌症治疗的进一步结论是，PI3K不是抑制转移形成的合适靶点，因为白细胞的迁移也受到影响，从而导致免疫防御功能障碍。
The polarization of tumor cells and leukocytes into a front end and a rear end is a crucial prerequisite for their autonomous, directed movement. Phosphatidylinositol 3-kinase (PI3K) is assumed to play an important role in this polarization process, whereas the results obtained with different cell types and different migration assays widely vary. Thus, we conducted a comparative study on the role of the PI3K in the locomotor activity and directionality of the migration of tumor cells on the example of MDA-MB-468 breast carcinoma cells in comparison with CTLs and neutrophil granulocytes. We used our well-established, collagen-based, three-dimensional migration assay for the investigation of the chemokinesis and chemotaxis of these cells. Our results show that the role of the PI3K in the regulation of migratory activity is distinct between the investigated cell types: the migration of CTLs and MDA-MB-468 cells was impaired by the inhibition of the PI3K with wortmannin, whereas neutrophil granulocytes were only slightly affected. However, neither cell type was impaired in the ability to respond chemotactically to gradients of ligands to G protein-coupled receptors. Thus, the PI3K contributes to the regulation of migratory activity but not to the directionality of migration of MDA-MB-468 breast carcinoma cells. As a further conclusion with regard to cancer treatment, the PI3K is not a suitable target for the inhibition of metastasis formation, because the migration of leukocytes is also affected, which leads to a dysfunction of the immune defense.