IL-17 and insulin/IGF1 enhance adhesion of prostate cancer cells to vascular endothelial cells through CD44-VCAM-1 interaction.

IL-17 and insulin/IGF1 enhance adhesion of prostate cancer cells to vascular endothelial cells through CD44-VCAM-1 interaction.
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DOI:
10.1002/pros.22971
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发表时间:
2015-06
期刊:
影响因子:
2.8
通讯作者:
You, Zongbing
You, Zongbing
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Chong;Zhang, Qiuyang;Liu, Sen;Parajuli, Keshab R.;Qu, Yine;Mei, Jiandong;Chen, Zhiquan;Zhang, Hui;Khismatullin, Damir B.;You, Zongbing

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外渗是癌症转移的关键步骤,其中血管内癌细胞与血管内皮细胞的粘附由细胞表面粘附分子控制。白细胞介素-17(IL-17)、胰岛素和胰岛素样生长因子1(IGF 1)在前列腺癌细胞与血管内皮细胞粘附中的作用尚不清楚,这是本研究的主题。使用流式细胞术和Western印迹分析,分析人脐静脉内皮细胞(HUVEC)和人前列腺癌细胞系(PC-3、DU-145、LNCaP和C4-2B)的血管细胞粘附分子1(VCAM-1)、整合素和分化簇44(CD 44)的表达。检测IL-17、胰岛素和IGF 1对前列腺癌细胞VCAM-1表达和与HUVECs粘附的影响。使用免疫沉淀试验评估VCAM-1和CD 44的相互作用。胰岛素和IGF 1与IL-17共同作用,增加HUVECs中VCAM-1的表达。PC-3、DU-145、LNCaP和C4-2B细胞表达β1整合素,但不表达α4整合素。CD 44在PC-3和DU-145细胞中表达,而在LNCaP和C4-2B细胞中不表达。当HUVEC用IL-17、胰岛素或IGF 1处理时,特别是用IL-17和胰岛素(或IGF 1)的组合处理时,PC-3和DU-145细胞与HUVEC的粘附显著增加。相反,LNCaP和C4-2B细胞与HUVEC的粘附不受用IL-17和/或胰岛素/IGF 1处理HUVEC的影响。PC-3细胞中表达的CD 44与HUVEC中表达的VCAM-1物理结合。CD 44-VCAM-1相互作用介导前列腺癌细胞与HUVEC之间的粘附。IL-17和胰岛素/IGF 1通过增加血管内皮细胞中VCAM-1的表达增强前列腺癌细胞与血管内皮细胞的粘附。这些发现表明IL-17可能与胰岛素/IGF 1共同作用促进前列腺癌转移。
Extravasation is a critical step in cancer metastasis, in which adhesion of intravascular cancer cells to the vascular endothelial cells is controlled by cell surface adhesion molecules. The role of interleukin-17 (IL-17), insulin, and insulin-like growth factor 1 (IGF1) in adhesion of prostate cancer cells to the vascular endothelial cells is unknown, which is the subject of the present study. Human umbilical vein endothelial cells (HUVECs) and human prostate cancer cell lines (PC-3, DU-145, LNCaP, and C4-2B) were analyzed for expression of vascular cell adhesion molecule 1 (VCAM-1), integrins, and cluster of differentiation 44 (CD44) using flow cytometry and Western blot analysis. The effects of IL-17, insulin and IGF1 on VCAM-1 expression and adhesion of prostate cancer cells to HUVECs were examined. The interaction of VCAM-1 and CD44 was assessed using immunoprecipitation assays. Insulin and IGF1 acted with IL-17 to increase VCAM-1 expression in HUVECs. PC-3, DU-145, LNCaP, and C4-2B cells expressed β1 integrin but not α4 integrin. CD44 was expressed by PC-3 and DU-145 cells but not by LNCaP or C4-2B cells. When HUVECs were treated with IL-17, insulin or IGF1, particularly with a combination of IL-17 and insulin (or IGF1), adhesion of PC-3 and DU-145 cells to HUVECs was significantly increased. In contrast, adhesion of LNCaP and C4-2B cells to HUVECs was not affected by treatment of HUVECs with IL-17 and/or insulin/IGF1. CD44 expressed in PC-3 cells physically bound to VCAM-1 expressed in HUVECs. CD44-VCAM-1 interaction mediates the adhesion between prostate cancer cells and HUVECs. IL-17 and insulin/IGF1 enhance adhesion of prostate cancer cells to vascular endothelial cells through increasing VCAM-1 expression in the vascular endothelial cells. These findings suggest that IL-17 may act with insulin/IGF1 to promote prostate cancer metastasis.
DOI: 10.1186/ar1038
发表时间: 2004
影响因子: 4.9
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