Effect of vascular endothelial growth factor and its receptor inhibitor on proliferation and invasion in bladder cancer.
BACKGROUND
Vascular endothelial growth factor (VEGF) and its receptors are major regulators of cancer cell growth and metastases. We investigated the association between serum VEGF levels and clinicopathological parameters in bladder cancer patients. We also evaluated the effects of VEGF and its receptor inhibitor on proliferation and invasion in bladder cancer cell lines.


METHODS
Serum VEGF levels were measured in 52 patients with bladder cancer and 45 healthy controls. In highly invasive bladder cancer cell lines (T-24, UMUC-3 and J82), we assessed the effect of VEGF on proliferation and invasion of bladder cancer cell lines. The effect of VEGF receptor (VEGFR) tyrosine kinase inhibitor against bladder cancer cell lines was also measured.


RESULTS
Serum levels of VEGF were significantly higher in patients with muscular invasive bladder cancer than in patients with superficial bladder cancer (p < 0.005). VEGF increased tumor proliferation in a dose-dependent manner in all cell lines. VEGFR-2 tyrosine kinase inhibitor inhibited proliferation in all three cell lines, and inhibited invasion in T24.


CONCLUSIONS
In bladder cancer, the serum VEGF level correlates significantly with muscular invasiveness. This study suggests that VEGF promotes tumor proliferation and invasion through VEGFR-2. VEGF-targeted therapy may be effective in treating invasive bladder cancers.
Nakanishi
Ryoichi
R
Department of Urology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan. ryo_yah3@yahoo.co.jp
Oka
Natsuo
N
Nakatsuji
Hiroyoshi
H
Koizumi
Takahiro
T
Sakaki
Manabu
M
Takahashi
Masayuki
M
Fukumori
Tomoharu
T
Kanayama
Hiro-omi
HO
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000097:blood / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
D002934:Cinnamates; C483044:SU 1498; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors