| Project/Area Number |
07671378
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
NISHINO Nobuhiko Hamamatsu University School of Medicine, 2nd Dept.of Surgery, Assistant Professor, 医学部附属病院, 講師 (80228197)
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| Co-Investigator(Kenkyū-buntansha) |
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)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| 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)
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| Keywords | u-PA / u-PAR / PAI / metastasis / u-PA / u-PAR / PA1 |
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| Research Abstract |
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.
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