Changes in the renin angiotensin system during the development of colorectal cancer liver metastases.
Changes in the renin angiotensin system during the development of colorectal cancer liver metastases.
复制标题
结直肠癌肝转移过程中肾素血管紧张素系统的变化
DOI：
10.1186/1471-2407-10-134
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发表时间：
2010-04-10
期刊：
影响因子：
3.8
通讯作者：
Christophi C
中科院分区：
文献类型：
--
作者：
Neo JH;Ager EI;Angus PW;Zhu J;Herath CB;Christophi C
在小鼠模型中，通过血管紧张素I转换酶（ACE）抑制作用阻断肾素血管紧张素系统（RAS）可减少结直肠癌（CRC）肝转移的生长。在这项工作中，我们确定了RAS的各种成分在肿瘤和肝脏中的表达，在这种疾病的进展。免疫组织化学和定量RT-PCR用于检测RAS在小鼠CRC肝转移模型中的表达。在未治疗（对照）小鼠和用ACE抑制剂卡托普利（750 mg/kg/天）治疗的小鼠中，在CRC肝转移发展的关键阶段分别评估CRC转移和肝组织。非肿瘤诱导（假手术）小鼠表明肿瘤对正常肝脏RAS的影响。多重比较的统计学显著性采用单因素方差分析，然后采用SAS/STAT软件进行Bonferroni调整。用卡托普利治疗的CRC肝转移灶体积明显减少。结直肠癌转移灶的局部RAS与周围肝脏不同，与肝脏相比，血管紧张素II 1型受体（AT 1 R）表达较低，但ANG-（1-7）受体（MasR）表达增加。AT 1 R定位于癌细胞和间质浸润细胞，而其他RAS受体仅在癌细胞中检测到。肿瘤诱导导致AT 1 R和ACE表达的初始增加，而在肿瘤生长的最后阶段，卡托普利治疗显着增加ACE表达。相反，卡托普利治疗降低AT 1 R和血管紧张素原的表达。这些结果表明，在携带肿瘤的卡托普利治疗的肝脏和CRC转移中RAS表达的显着变化。这些数据表明存在肿瘤特异性RAS，其可以通过RAS阻断独立靶向。
Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade.
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卡托普利在人肾细胞癌的异种移植模型中抑制肿瘤生长。
影响因子：
8.8
作者：
Hii, SI;Nicol, DL;Gotley, DC;Thompson, LC;Green, MK;Jonsson, JR
通讯作者：
Jonsson, JR
影响因子：
20.1
作者：
Donoghue, M;Hsieh, F;Acton, S
通讯作者：
Acton, S
影响因子：
168.9
作者：
Lever, AF;Hole, DJ;Robertson, JWK
通讯作者：
Robertson, JWK
影响因子：
8.3
作者：
Freeman, EJ;Chisolm, GM;Tallant, EA
通讯作者：
Tallant, EA
影响因子：
4.7
作者：
Gallagher, PE;Tallant, EA
通讯作者：
Tallant, EA