The renin angiotensin system regulates Kupffer cells in colorectal liver metastases
Shu Wen Wen, Eleanor I Ager, Jaclyn Neo, Christopher Christophi
CANCER BIOLOGY & THERAPY | LANDES BIOSCIENCE | Published : 2013
Blockade of the renin angiotensin system (RAS) can inhibit tumor growth and this may be mediated via undefined immunomodulatory actions. This study investigated the effects of RAS blockade on liver macrophages (Kupffer cells; KCs) in an orthotopic murine model of colorectal cancer (CRC) liver metastases. Here we showed that pharmacological targeting of the RAS [ANG II (31.25 µg/kg/h i.p.), ANG-(1-7) (24 µg/kg/h i.p.) or the ACE inhibitor; captopril (750 mg/kg/d i.p.)] altered endogenous KC numbers in the tumor-bearing liver throughout metastatic growth. Captopril, and to a lesser extent ANG-(1-7), increased KC numbers in the liver but not tumor. KCs were found to express the key RAS componen..View full abstract
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This work was supported by Cancer Australia's Priority-driven Collaborative Cancer Research Scheme (co-funded by Cancer Australia and Cure Cancer Australia Foundation) and by the Cancer Council of Victoria. EIA was supported by an NHMRC Post-doctoral Training Award. SWW and JN were supported by an Australian Rotary Health Research Fund PhD Scholarship. TF aided in editing the manuscript. SWW performed experimental and statistical analysis and drafted the manuscript. EIA and SWW contributed equally to experimental design and protocol optimization. JN contributed to the RAS treatment and tissue collection. EIA and CC reviewed the manuscript and aided in the development of the concepts tested.