SDF-1alpha concentration dependent modulation of RhoA and Rac1 modifies breast cancer and stromal cells interaction.
SDF-1alpha concentration dependent modulation of RhoA and Rac1 modifies breast cancer and stromal cells interaction.
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DOI：
10.1186/s12885-015-1556-7
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发表时间：
2015-08-01
期刊：
影响因子：
3.8
通讯作者：
Rafii A
中科院分区：
文献类型：
--
作者：
Pasquier J;Abu-Kaoud N;Abdesselem H;Madani A;Hoarau-Véchot J;Thawadi HA;Vidal F;Couderc B;Favre G;Rafii A
SDF-1 α与其受体CXCR 4的相互作用在许多实体瘤的远处转移中起作用。这种相互作用增加了从主要地点的迁移以及在遥远地点的归巢。在此，我们研究了SDF-1α如何通过调节RhoGTPases来调节癌细胞的迁移和粘附。我们发现，不同浓度的SDF-1α调节癌细胞粘附和迁移的平衡。在50和100 ng/ml SDF-1α时，迁移增加;但在200 ng/ml时，迁移减少。200 ng/ml的SDF-1α处理显著增加乳腺癌细胞与BMHC之间的粘附，并使用针对CXCR 4的阻断性单克隆抗体降低粘附。我们发现在低浓度SDF-1α时，RhoA被激活并过表达，而在高浓度Rac 1则促进SDF-1α介导的细胞粘附。我们得出结论，SDF-1α浓度调节乳腺癌细胞的迁移和粘附，通过控制RhoGTPases的表达和激活。本文的在线版本（doi：10.1186/s12885-015-1556-7）包含补充材料，可供授权用户使用。
The interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors. This interaction increases migration from primary sites as well as homing at distant sites. Here we investigated how SDF-1α could modulate both migration and adhesion of cancer cells through the modulation of RhoGTPases. We show that different concentrations of SDF-1α modulate the balance of adhesion and migration in cancer cells. Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml. The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4. We showed that at low SDF-1α concentration, RhoA was activated and overexpressed, while at high concentration Rac1 was promoting SDF-1α mediating-cell adhesion. We conclude that SDF-1α concentration modulates migration and adhesion of breast cancer cells, by controlling expression and activation of RhoGTPases. The online version of this article (doi:10.1186/s12885-015-1556-7) contains supplementary material, which is available to authorized users.