Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

BMC Cancer

Research Article

Peter W Angus¹  Chandana B Herath¹  Jin Zhu²  Christopher Christophi²  Jaclyn H Neo²  Eleanor I Ager² 

[1] Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia;Department of Surgery, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia;

关键词: Captopril;    Angiotensinogen;    Renin Angiotensin System;    Captopril Treatment;    Renin Angiotensin System Blockade;   

DOI  :  10.1186/1471-2407-10-134

 received in 2009-11-12, accepted in 2010-04-10,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundBlockade 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.MethodsImmunohistochemistry 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.ResultsReduced 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.ConclusionsThese 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.

【 授权许可】

CC BY   
© Neo et al; licensee BioMed Central Ltd. 2010