| Project/Area Number |
12470234
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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 |
ISHII Seiichi Tohoku University Hospital Research Associate, 医学部附属病院, 助手 (60221066)
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| Co-Investigator(Kenkyū-buntansha) |
MIZOI Takayuki Tohoku University Hospital Research Associate, 医学部附属病院, 助手 (90271949)
SATO Yasufumi Tohoku University Institute of Development Aging and Cancer Professor, 加齢医学研究所, 教授 (50178779)
KAMEOKA Junichi Tohoku University Hospital Research Associate, 医学部附属病院, 助手 (30261621)
SAITO Kazuya Tohoku University Hospital Research Associate, 医学部附属病院, 助手 (30343049)
大谷 明夫 東北大学, 大学院・医学系研究所, 助教授 (30133987)
斎藤 一也 東北大学, 医学部・附属病院, 助手
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | colorectal cancer / metastasis / angiogenesis / lymphangiogenesis / VEGFR-3 / VEGF-C / VEGF-D / CD44 / GFP / 生体顕微鏡 / 血管内皮前駆細胞 / NOD / SCID |
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| Research Abstract |
[Purpose] The purpose of this project was to establish and analyze the "in vivo human tumor angiogenesis model".
[Materials and Methods] Four human colorectal carcinoma (CRC) cell lines, CCL188, Colo320, MIP101 and Clone A, were orthotopically implantated in the cecum of nude. Expression of angiogenic and lymphangiogenic factors in the CRC cells were analyzed by RT-PCR, ELISA and immunohistochemistry. Tumor angiogenesis was observed by CD31 immune-staining and intravital fluorescence microscopy (IVFM) with stable GFP-transfectants of each cell line. Tumor lymphangiogenesis was also examined with anti-VEGFR3 antibody.
[Results] When inoculated into the spleens of nude mice CCL188 and CX-1 produced tumors in the liver in almost 100% of mice whereas the other two cell lines rarely formed hepatic tumors. When human CRC cells were implanted orthotopically in nude mice Matrigel-suspended cells produced local tumors with significantly higher efficacy than the cells suspended in PBS or Cellmatri
… More
x. Matrigel also enhanced spontaneous metastasis to the liver only by the two highly metastatic CRC cell lines. However, orthotopic implantation of CRC cells with Matrigel did not increase peritoneal metastasis. All the four CRC cell lines released VEGF with different extents while CCL188 and CX-1 did greater amount than did by MTP101 and Clone A. Anti-mouse CD31 immno-staining showed induction of tumor angiogenesis 3 days after implantation of CRC cells. The results were well compatible with the findings of tumor angiogenesis observed under the IVFM with GFP transfectants. The two highly metastatic cell lines induced higher density of microvessels than the other two cell lines did. Expressions of VEGF-C and VEGF-D in CRC cells showed correlation to lymph vessel density but did not correlate to the metastatic ability to lymph nodes.
[Conclusions] VEGF, that induces tumor angiogenesis in CRC cells, may have effects on the production of hepatic metastasis. In contrast, VEGF-C and VEGF-D, that enhance tumor lymphangiogenesis, may not decide the metastatic ability to lymph nodes. Less
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