| Budget Amount *help |
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
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| Research Abstract |
The cytokines production, TN7F- alpha and IL-1 beta were detected during the mixed leukocytes tumor cell culture (MLTC) (co-culture of pancreatic cancer cells with perpheral blood mononuclear leukocytes ; MNL from healthy volunteers), and these cytokines were mainly produced by monocytes. They may activate endothelial cells and induce ELAM-1 expression on them which will play an important role in cancer cell-endothelial cell adhesion and liver metastasis. Consequently, the expression of adhesion molecules involved in immune reaction on cancer cells was investigated using three human pancreatic cancer cells, SW1990 (highly liver metastatic), CAPAN-2 (low metastatic) and PANC-1 (no metastatic). While the expressions of HLA class I antigen were detected on all cells, ICAM-1 expression was low in SW1990 contrary to its metastatic potentia. According to this result, MNL adhesion to SW1990 and cytotoxicity of SW1990 by MNL were minimum and cell escape of SW1990 from immune effector cells suc
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h as NK, LAK cells which use ICAM-1/LFA-1 system in cancer cell recognition must be involved in development of metastasis. Next investigating the relationship between ICAM-1 expression and clinicopathological factors by immunochemical study on surgical specimens, histological type and existence of lymphnode's metastasis or invasion to portal system have no relationship, but liver metastasis were highly found in ICAM-1 negative cases compared with positive case. ICAM-1 expressions on cancer cell surface were increased in dose dependent fashion by treatment with TNF- alpha except for SW1990, on the other hand TGF- beta1) significantly decreased ICAM-1 expression on all cells and lymphocyte's adhesion and cytotoxicity to cancer cells. Finally as other functional effects of TGF- beta1 in invasion and metastasis were investigated, it increase protenase productions such as MMP-2 and u-PA, in vitro invasion and in vivo liver metastasis of metastatic SW1990 and CAPAN-2. These findings suggested that TGF- beta1 may play important roles in liver metastasis of pancreatic cancer not only by suppressing host immune function but also by making cancer cells escape from effector cells through inhibiting ICAM-1 expression and increasing invasive and metastatic potential in autocrine or paracrine fashion. New therapeutic application to inhibit liver metastasis using neubizing TGF- beta1 antibody or drugs to decrease the production of TGF- beta1 should be investigated in future study. Less
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