| Co-Investigator(Kenkyū-buntansha) |
BEPPU Tomoe School of Medicine, Juntendo University, Associate Professor, 医学部, 助教授 (00111542)
TSUIJI Makoto Graduate school of Pharmaceutical Sciences, The University of Tokyo, Research Associate, 大学院・薬学系研究科, 助手 (90302611)
HIGASHI Nubuaki Graduate school of Pharmaceutical Sciences, The University of Tokyo, Lecturer, 大学院・薬学系研究科, 講師 (40302616)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Research Abstract |
1. Human pancreatic carcinoma cell lines (MIA PaCa-2, Hs776T, PANC-1, MDA Panc 3, MDA Panc 28, SU86.86, HPAF-II, AsPC-1, Capan-1, and HPAC) were tested for their capacity to generate hepatic metastataic following intrasplenic injections in athymic nude mice. Only four cell line (HPAF-II, AsPC-1, Capan-1, and HPAC) were shown to produce hepatic metastasis. These four cell lines were subjected to in vivo selections for increased metastatic potentials following intrasplenic injections. However, cells grown out from metastases did not show increase in the metastatic potential.
2. Because these four cell lines (HPAF-II, AsPC-1, Capan-1, and HPAC) were shown to metastasize to the liver after intra-pancreatic transplantations, in vivo selections with the orthotopic transplantation were also conducted. Highly metastatic variants, were not generated by this selection.
3. These results indicated that characterization of cellular and molecular determinants of highly metastatic pancreatic carcinoma
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cells should be conducted through selections of poorly metastatic variants from these four highly metastatic variant cell lines. Also, it is suggested that comparisons between these four metastaic cells and rest (six cell lines) should prove to be useful.
4. A pair of pathological specimens from noninvasive and highly invasive tumors adjacent to each other was compared for the gene expression by the use of expression arrays. Nine genes (MAPkinase kinase-5、 protooncogene c-src、 aggrecan 1、chondroitin sulfate coreprotein-1、Visican isohomes、BM-40、thrombospondin-1 precursor、TIMP-1、procollagen C-protein) were identified to be higher in the expression level in the non-invasive tumor than in the adjacent invasive tumor. However, the levels were not always low in the invasive tumors when nine pathological specimens were compared, i.e. the differential expression between non-invasive and highly malignant pancreatic carcinoma cells was not always the case.
5. Dr. Isaiah J. Fidler's group at the University of Texas M. D. Anderson Cancer Center established highly metastatic variant cells of human pancreatic COLO357 carcinoma cells. One of these cell lines, L3.6pl cells, was shown to be more metastatic after orthotopic transplantation into pancreas of nude mice than the parental FG cells. As a collaborative effort, difference in the level of gene expression between these two cells was examined by Takara Intelligene Microarray. Thirty three genes were found to be expressed more than three times higher in L3.6pl cells as compared to parental FG cells. Less
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