Activation of invasiveness of cervical carcinoma cells by angiotensin II.
OBJECTIVE
Angiotensin II recently has been reported to promote the growth of several kinds of cells. In this study, we investigated the effect of angiotensin II on cervical carcinoma cells.


METHODS
The expression of angiotensin II type I receptor was examined by immunohistochemistry in normal and neoplastic cervical tissues. Invasion assay was examined in Siha cells (cervical squamous cell carcinoma) and vascular endothelial growth factor levels were assayed with a vascular endothelial growth factor enzyme-linked immunosorbent assay kit.


RESULTS
Mean staining intensity level was stronger in invasive carcinoma cells than in normal, dysplasia, and carcinoma in situ tissues. Angiotensin II induced the secretion of vascular endothelial growth factor from Siha cells. Furthermore, angiotensin II promoted the invasive potential of Siha cells. These effects were reversed by the addition of anti-human vascular endothelial growth factor antibody and candesartan (antagonist of angiotensin II type I receptor).


CONCLUSIONS
Angiotensin II is involved in the progression of cervical carcinoma, because it induces the secretion of vascular endothelial growth factor through angiotensin II type I receptor, which results in the increased invasiveness of carcinoma cells.
Kikkawa
Fumitaka
F
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan. kikkawaf@med.nagoya-u.ac.jp
Mizuno
Mika
M
Shibata
Kiyosumi
K
Kajiyama
Hiroaki
H
Morita
Takanori
T
Ino
Kazuhiko
K
Nomura
Seiji
S
Mizutani
Shigehiko
S
D000804:Angiotensin II / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011336:Probability; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis; D012016:Reference Values; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000187:drug effects
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D040262:Receptors, Vascular Endothelial Growth Factor