Analysis of possible role of u-PAR and PAI in cancer metastasis
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Hamamatsu University School of Medicine|
NISHINO Nobuhiko Hamamatsu University School of Medicine, 2nd Dept.of Surgery, Assistant Professor, 医学部附属病院, 講師 (80228197)
KONNO Hiroyuki Hamamatsu University School of Medicine, 2nd Dept.of Surgery, Assistant Professo, 医学部附属病院, 講師 (00138033)
URANO Tetsumei Hamamatsu University School of Medicine, 2nd Dept.of Physiology, Associate Proff, 医学部, 助教授 (50193967)
|Project Period (FY)
1995 – 1997
Completed(Fiscal Year 1997)
|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1996 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1995 : ¥500,000 (Direct Cost : ¥500,000)
|Keywords||u-PA / u-PAR / PAI / metastasis / u-PA / u-PAR / PA1|
The role of u-PA,u-PAR and PAI for invasion and metastasis of cancer was investigated.
a) clinical study
(1) The levels of u-PA,PAI-1 and PAI-2 in cancer tissues of gastrointestinal tract showed significantly higher than those of adjacent normal mucosa.
(2) High u-PA group showed poor prognosis in colorectal cancer.
(3) Tumors with lower PAI-2 levels tended to metastasize to remote lymph nodes suggesting that PAI-2 might have a role to suppress lymph node metastasis.
(4) We succeeded to establish human colon cancer xenografts which contained different levels of u-PA from surgical specimens.
b) in vitro study
Alterations of cell proliferation and invasion by u-PA,PAI-1 and PAI-2 were investigated using human tumor cell lines.
The results showed that u-PA accelerated cell proliferation in a dose dependent manner, and PAI-2 suppressed in dose and time dependent manner. Moreover, u-PA accelerated cell invasion, though PAI-1 and PAI-2 suppressed it significantly.
c) in vivo study
The effects of PAI-1 and PAI-2 on tumor growth and metastasis were investigated using spontaneous metastatic models of human colon carcinoma.
The results showed that the size of primary tumor was significantly lower in PAI-2 treated group than those in control and PAI-1 treated groups, and the rate of liver metastasis was lower in PAI-1 and PAI-2 treated groups than that in control group.
We conclude that PAI-2 may suppress tumor growth and metastasis.
Research Output (1results)