2001 Fiscal Year Final Research Report Summary
Analysis of micromechanisms of metastasis using NOD/SCID-hu and GFP-transfectant human colorectal carcinoma cells
| Project/Area Number |
11557082
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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 | 展開研究 |
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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) |
SHIIBA Kenichi Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90196345)
OTANI Haruo Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (30133987)
SATO Yasufumi Tohoku University, Research Institute of Aging and Cancer, Professor, 加齢医学研究所, 教授 (50178779)
ISHII Keiko Tohoku University, Hospital, Lecturer, 医学部・附属病院, 講師 (00291253)
MIZOI Takayuki Tohoku University, Hospital, Research Associate, 医学部・附属病院, 助手 (90271949)
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| Project Period (FY) |
1999 – 2001
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| Keywords | colorectal cancer / metastasis / intravital microscopy / GFP / angiogenesis |
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| Research Abstract |
[Purpose] The purpose of this project was to study the micromechanisms of cancer metastasis. [Materials and Methods] Four human colorectal carcinoma (CRC) cell lines, CCL188, CX-1, MIP101 and Clone A, were used. Orthotopic implantation of CRC cells in the cecum of nude mice were carried out with the CRC cells suspeneded either n PBS, Matrigel or Cellmatrix (type I collagen). Expression of angiogenic factors in the CRC cells were analyzed by RT-PCR, ELISA and immunohistochemistry. Tumor angiogenesis was observed by CD31 immuno-staining and intravital fluorescence microscopy (IVFM) with stable GFP-transfectants of each cell line. [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
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or Cellmatrix. 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. AH the four CRC cell lines released VEGF with different extents while CCL188 and CX-1 did greater amount than did by MIP101 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. Co-implantation of human CRC cells with normal human bone marrow cells did not induce tumor vessels of human endothelial cell origin. [Conclusions] Matrigel enhances local tumor growth and metastasis of orthotopically implanted human CRC cells in nude mice. There may be a correlation between the production of VEGF by CRC cells and the density of microvessels induced in the tumors. Less
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Research Products
(8 results)
