| Co-Investigator(Kenkyū-buntansha) |
OGASAWARA Sachiko Kurume University, School of Medicine, Fellow, 医学部, 助手 (40258405)
YANO Hirohisa Kurume University, School of Medicine, Instructor, 医学部, 講師 (40220206)
IEMURA Akihiro Kurume University, School of Medicine, Fellow (40212724)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
The mechanisms of invasion and metastasis of hepatocellular carcinoma (HCC) were studied in the present study. [1] In the first part of the experiment, we confirmed an increase of chemokinesis and chemotaxis Induced by deletion type hepatocyte growth factor in 2 of 10 human HCC cell lines. HCC cells in the human liver tissue could also contact to dHGF with a concentration gradient because HGF could be released from endothelial cells in and around the HCC nodules or various mesenchymal cells in the surrounding non-HCC tissues. The acceleration effect on cell movement, or the chemotactic effects, of dHGF would be involved in the mechanism of invasion and metastasis of the HCC cells. [2] Next, we investigated expressions of matrix metalloproteinases (MMPs) (MMP-2, MMP-7, MMP-9, MT1-MMP, MT2-MMP, and MT3-MMP) and tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2) in human HCC and non-HCC tissues by using immunohistochemical technique. HCC cells expressed MMP-2, MMP-9, TIMP-2, MT3-MM
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P at high frequency and high level. The expression of MMPs and TIMPs was observed in HCC cells, hepatocytes, biliary epithelial cells, Kupffer cells, endothelial cells, and fibrous stroma. Total amounts and active form MMP-2 were measured by using enzyme-linked immunosorbent assay. There was no difference in the total MMP expression levels between HCC and non-HCC tissues, but the expression of active form MMP-2 tended to be higher in the HCC tissues than in non-HCC tissues. [3] Expression of MMPs and TIMPs, and its regulation by cytokines and growth factors were examined in 11 HCC by using flow cytometry. All cell lines expressed relatively high levels of MMP-2 and MMP-9, and low levels of TIMP-2 and MT1-MMP.most of the cell lines did not express MMP-7, TIMP-1, MT2-MNP, and MT3-MMP.In 7 of the 11 cells lines, the expression of MMP-2 was attenuated by most of the cytokine and growth factor treatments. The results MMP-2, MMP-9, TIMP-2, and MT1-MMP of the 11 cell lines showed good agreement with those of HCC tisseue. In conclusion, the present study suggested a possibility that the expression of dHGF and MMPs in the HCC stromal tissues and in the non-HCC tissues play an important role in invasion and metastasis of HCC. Less
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