Molecular basis for the involvement of thymidine phosphorylase in cancer invasion.
Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), has been implicated in bladder cancer angiogenesis and invasion. However, the molecular basis of its role in invasion remains unclear. We investigated the expression of TP and 10 invasion-related genes in bladder cancers from 72 randomly selected patients by real-time two-step RT-PCR assay. We found that the expression levels of TP, MMP-9, uPA, and MMP-2 were significantly higher in invasive tumors than those in superficial tumors. Also, the expression level of TP significantly correlated with that of uPA, MMP-1, MMP-9, PAI-1 and VEGF. KK47/TP cells, bladder cancer cells that overexpress TP, had a higher expression of MMP-7 and MMP-9 than KK/CV cells that express lower level of TP in hypoxic condition. PC/TP cells, prostate cancer cells that overexpress TP, also had a higher expression of MMP-1 and MMP-7 than PC/CV cells that express no detectable TP. Taken together these data indicate that TP enhances the invasion of tumor cells through the induction of invasion-related genes.
Gotanda
Takenari
T
Department of Urology, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
Haraguchi
Misako
M
Tachiwada
Tokushi
T
Shinkura
Reiko
R
Koriyama
Chihaya
C
Akiba
Suminori
S
Kawahara
Motoshi
M
Nishiyama
Kenryu
K
Sumizawa
Tomoyuki
T
Furukawa
Tatsuhiko
T
Mimata
Hiromitsu
H
Nomura
Yoshio
Y
Akiyama
Shin-Ichi
S
Nakagawa
Masayuki
M