The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer.
Angiotensin II (AngII) is a multifunctional bioactive peptide and previous studies have shown that the renin-angiotensin system (RAS) of both host and tumor are important in tumor growth and angiogenesis in lung cancer. Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS, with 42% amino acid homology to ACE. However, the expression and function of ACE2 in non-small cell lung cancer (NSCLC) are still unclear. In the present study, we analyzed ACE2 expression in NSCLC tissue by Western blot analysis and immunohistochemistry. AngII concentrations in the tissue homogenate were also detected using radio-immunoassay. We also examined the function of ACE2 by transducing A549 cells with MSCV-ACE2. We have shown for the first time that ACE2 expression decreased in NSCLC tissue in which AngII was higher than the matching non-malignant tissues. A concentration of 10(-6) mol/l of AngII significantly increased expression of vascular endothelial growth factor a (VEGFa) and AT1-R and decreased ACE2 expression. We also found that overexpression of ACE2 may have a protective effect by inhibiting cell growth and VEGFa production in vitro. ACE2 may become a target of novel strategies to treat NSCLC.
Feng
Yun
Y
Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
Wan
Huanying
H
Liu
Jialin
J
Zhang
Ruifeng
R
Ma
Qinyun
Q
Han
Bing
B
Xiang
Yi
Y
Che
Jiaming
J
Cao
Huangming
H
Fei
Xiaochun
X
Qiu
Weicheng
W
D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D044140:Receptor, Angiotensin, Type 1; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2