Angiotensin II augmented migration and invasion of choriocarcinoma cells involves PI3K activation through the AT1 receptor.
While angiotensin II (Ang II) has been shown to inhibit migration of extravillous trophoblasts via plasminogen activator inhibitor-1 (PAI-1) activation, it has remained unclear whether it stimulates or inhibits malignant behavior of choriocarcinoma cells. Since we previously found an involvement of the renin-angiotensin system (RAS) in the proliferative potential in choriocarcinoma cells (BeWo), mediated via the Ang II type 1 receptor (AT1R), in the present study we investigated the effects of Ang II on choriocarcinoma cell migration/invasion in vitro using Transwell cell culture chambers. Ang II (10(-8)M) promoted migration and invasion by a choriocarcinoma cell line and augmented random cell mobility on checkerboard analysis. Immunoblotting showed Ang II to activate the phosphorylation of FAK and Akt in BeWo cells. Furthermore Ang II effects on cell migration were abolished by a selective AT1R antagonist and a phosphatidylinositol 3-kinase (PI3K) inhibitor. The present results suggest that Ang II-induced migration and invasion of choriocarcinoma cells probably involves PI3K following binding to the AT1R.
Ishimatsu
S
S
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Itakura
A
A
Okada
M
M
Kotani
T
T
Iwase
A
A
Kajiyama
H
H
Ino
K
K
Kikkawa
F
F
D000804:Angiotensin II / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002822:Choriocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000804:Angiotensin II; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents