The Ron receptor tyrosine kinase positively regulates angiogenic chemokine production in prostate cancer cells.
The Ron receptor tyrosine kinase positively regulates angiogenic chemokine production in prostate cancer cells.
复制标题
DOI：
10.1038/onc.2009.331
复制
发表时间：
2010-01-14
期刊：
影响因子：
8
通讯作者：
Waltz, S. E.
中科院分区：
文献类型：
--
作者：
Thobe, M. N.;Gurusamy, D.;Pathrose, P.;Waltz, S. E.
最近在多种人类癌症中发现了 Ron 受体酪氨酸激酶的过度表达。然而，没有研究检查前列腺肿瘤发生过程中 Ron 受体的表达或功能。我们在此报告，与正常前列腺或良性前列腺增生相比，Ron 在人前列腺腺癌和转移性淋巴结中高表达。此外，我们发现 Ron 在 PC-3 和 DU145 前列腺癌细胞系中过表达，并且前列腺癌细胞产生的血管生成趋化因子的水平与 Ron 表达呈正相关。 PC-3 或 DU145 细胞中 Ron 的敲低会导致血管生成趋化因子产生显着减少，并与转录因子 NF-kappaB 的激活减少相关。此外，LNCaP 细胞中 Ron 的外源过度表达足以诱导血管生成趋化因子显着增加，而这种增加可以通过抑制 NF-kappaB 信号传导来消除。鉴于血管生成趋化因子的功能在新血管的发育中很重要，我们还检查了 Ron 调节内皮细胞迁移的能力。我们的数据表明，与体外表达 Ron 的细胞相比，前列腺癌细胞中 Ron 的敲低不仅会导致内皮细胞趋化性显着降低，而且在体内原位移植到前列腺后会减少肿瘤生长并降低微血管密度。总的来说，我们的数据表明，Ron 受体通过调节血管生成趋化因子的产生和随后的内皮细胞募集来调节前列腺肿瘤的生长。
Overexpression of the Ron receptor tyrosine kinase has recently been shown in a wide variety of human cancers. However, no studies have examined Ron receptor expression or function during prostate tumorigenesis. We report here that Ron is highly expressed in human prostate adenocarcinoma and metastatic lymph nodes compared to normal prostate or benign prostate hyperplasia. Furthermore, we show that Ron is overexpressed in PC-3 and DU145 prostate cancer cell lines, and that levels of angiogenic chemokines produced by prostate cancer cells positively correlates with Ron expression. Knockdown of Ron in PC-3 or DU145 cells results in a significant decrease in angiogenic chemokine production and is associated with decreased activation of the transcription factor NF-kappaB. Moreover, exogenous overexpression of Ron in LNCaP cells is sufficient to induce a significant increase in angiogenic chemokines that can be abrogated by inhibition of NF-kappaB signaling. Given that the function of angiogenic chemokines is important in the development of new blood vessels, we also examined the ability of Ron to modulate endothelial cell migration. Our data show that knockdown of Ron in prostate cancer cells results both in significantly less endothelial cell chemotaxis compared to Ron-expressing cells in vitro as well as in reduced tumor growth and decreased microvessel density following orthotopic transplantation into the prostate in vivo. In total, our data suggest that the Ron receptor is important in modulating prostate tumor growth by modulating angiogenic chemokine production and subsequent endothelial cell recruitment.
登录
查看更多内容
影响因子：
4.8
作者：
Dhanasekaran, SM;Dash, A;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM
影响因子：
8
作者：
Maggiora, P;Marchio, S;Comoglio, PM
通讯作者：
Comoglio, PM
DOI：
10.2217/14796694.3.4.441
发表时间：
2007-08-01
期刊：
Future oncology (London, England)
影响因子：
--
作者：
Leonis, Mike A;Thobe, Megan N;Waltz, Susan E
通讯作者：
Waltz, Susan E
影响因子：
3.7
作者：
Chen, YQ;Zhou, YQ;Wang, MH
通讯作者：
Wang, MH
DOI：
10.1161/atvbaha.108.162925
发表时间：
2008-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Keeley EC;Mehrad B;Strieter RM
通讯作者：
Strieter RM