PMID- 15814650
OWN - NLM
STAT- MEDLINE
DCOM- 20050808
LR  - 20220408
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 11
IP  - 7
DP  - 2005 Apr 1
TI  - Functional expression of the angiotensin II type 1 receptor in human ovarian 
      carcinoma cells and its blockade therapy resulting in suppression of tumor 
      invasion, angiogenesis, and peritoneal dissemination.
PG  - 2686-94
AB  - PURPOSE: Angiotensin II is a bioactive peptide of the renin-angiotensin system, 
      acting not only as a vasoconstrictor but also as a growth promoter via 
      angiotensin II type 1 receptors (AT1R). The present study examined AT1R 
      expression in human ovarian carcinoma and attempted to determine whether AT1R 
      blocker could suppress the tumor progression. EXPERIMENTAL DESIGN: Expression of 
      AT1R, vascular endothelial growth factor (VEGF), and CD34 was 
      immunohistochemically analyzed in ovarian tumor tissues (n=99). Effects of AT1R 
      blocker on invasive potential and VEGF secretion in ovarian cancer cells were 
      examined in vitro. Effects of AT1R blocker in vivo were evaluated in a mouse 
      model of peritoneal carcinomatosis. RESULTS: AT1R was expressed in 57 of 67 (85%) 
      invasive ovarian adenocarcinomas and 12 of 18 (66%) borderline malignant tumors 
      but in only 2 of 14 (14%) benign cystadenomas. In invasive carcinomas, VEGF 
      expression intensity and intratumor microvessel density were significantly higher 
      in cases that were strongly positive for AT1R (n = 37) compared with those in 
      cases weakly positive (n = 20) or negative (n = 10) for AT1R. Angiotensin II 
      significantly enhanced the invasive potential and VEGF secretion in AT1R-positive 
      SKOV-3 ovarian cancer cells, both of which were completely inhibited by the AT1R 
      blocker candesartan. Administration of candesartan into SKOV-3-transplanted 
      athymic mice resulted in the reduction of peritoneal dissemination, decreased 
      ascitic VEGF concentration, and suppression of tumor angiogenesis. CONCLUSIONS: 
      AT1R is functionally expressed in ovarian carcinoma and involved in tumor 
      progression and angiogenesis. AT1R blockade therapy may become a novel and 
      promising strategy for ovarian cancer treatment.
FAU - Suganuma, Takayasu
AU  - Suganuma T
AD  - Department of Obstetrics and Gynecology, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
FAU - Ino, Kazuhiko
AU  - Ino K
FAU - Shibata, Kiyosumi
AU  - Shibata K
FAU - Kajiyama, Hiroaki
AU  - Kajiyama H
FAU - Nagasaka, Tetsuro
AU  - Nagasaka T
FAU - Mizutani, Shigehiko
AU  - Mizutani S
FAU - Kikkawa, Fumitaka
AU  - Kikkawa F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Antigens, CD34)
RN  - 0 (Benzimidazoles)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Tetrazoles)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 11128-99-7 (Angiotensin II)
RN  - S8Q36MD2XX (candesartan)
SB  - IM
MH  - Adenocarcinoma/metabolism/pathology/prevention & control
MH  - Angiotensin II/pharmacology
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology/therapeutic use
MH  - Animals
MH  - Antigens, CD34/analysis
MH  - Benzimidazoles/pharmacology/therapeutic use
MH  - Biphenyl Compounds
MH  - Cell Line, Tumor
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasm Invasiveness/prevention & control
MH  - Neovascularization, Pathologic/prevention & control
MH  - Ovarian Neoplasms/metabolism/pathology/*prevention & control
MH  - Peritoneum/*drug effects/pathology
MH  - Receptor, Angiotensin, Type 1/*biosynthesis/genetics
MH  - Tetrazoles/pharmacology/therapeutic use
MH  - Vascular Endothelial Growth Factor A/analysis/metabolism
MH  - Xenograft Model Antitumor Assays
EDAT- 2005/04/09 09:00
MHDA- 2005/08/09 09:00
CRDT- 2005/04/09 09:00
PHST- 2005/04/09 09:00 [pubmed]
PHST- 2005/08/09 09:00 [medline]
PHST- 2005/04/09 09:00 [entrez]
AID - 11/7/2686 [pii]
AID - 10.1158/1078-0432.CCR-04-1946 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2005 Apr 1;11(7):2686-94. doi: 10.1158/1078-0432.CCR-04-1946.