| Project/Area Number |
15390370
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
MIZOI Takayuki (2005) Tohoku University, Hospital, Lecturer, 病院, 講師 (90271949)
三浦 康 (2004) 東北大学, 病院, 助手 (40282074)
石井 誠一 (2003) 東北大学, 医学部附属病院, 助手 (60221066)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Yasufumi Tohoku University, Institute of Development Aging and Cancer, Professor, 加齢医学部研究所, 教授 (50178779)
KASAI Noriyuki Tohoku University, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (60001947)
KOBAYASHI Terutada Tohoku University, Hospital, Research Associate, 助手 (30312143)
椎葉 健一 東北大学, 大学院・医学系研究科, 助教授 (90196345)
溝井 賢幸 東北大学, 病院・助手 (90271949)
三浦 康 東北大学, 医学部附属病院, 助手 (40282074)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | colorectal cancer / lymph node metastasis / lymphangiogenesis / CD44 / hyarulonic acid / cell attachment / microarray |
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| Research Abstract |
We investigated the interaction between CD44 and its ligand, hyaluronic acid, on lymph node metastasis of colorectal cancers. In 90% of nude mice, lymph node metastasis was established by alloic transplantation of LS174T and LS174T-NEO, which expressed high levels of CD44. In contrast, Colo320 and LS174T-AS2, which were transfected with antisense CD44 gene, had no expressions of CD44 and never metastasized to lymph nodes by alloic transplantation in nude mice. In immunohistochemistry of lymphatic vessels, LS174T-NEO showed marked lymphatic invasion, in contrast to minimal lymphatic invasion in LS174T-AS2 and Colo320. LS174T and LS174T-NEO widely attached to normal lymph nodes, and it was inhibited by anti-hyaluronic acid processing. On the other hand, the attachment to lymph nodes was significantly reduced in LS174T-AS2.
We evaluated the ability of colorectal cancer cell lines on metastasis to lymph nodes, and metastatic (or anti-metastatic) genes were screened by cDNA microarray. Twenty three of human colorectal cancer cell lines were investigated on the lymph node metastasis in alloic transplantation model and the incidence of metastasis was varied widely as follows : KM12c 100%(7/7), CloneA 100%(9/9), HT29 94.4%(17/18),..., SW1116 25%(2/8), DLD1 0%(0/13). Cell lines were divided into three groups (high, middle and low) according to the incidence of lymph node metastasis. Based on cDNA microarray analysis together with in vivo experiments, 107 candidates of metastasis-related genes were extracted. The expression levels of some of those genes were confirmed elevated or depressed with real-time RT-PCR as well. Further, there was a relationship between expression levels of candidate genes and clinical lymph node metastasis in colorectal cancers.
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