1993 Fiscal Year Final Research Report Summary
Effects of Epidermal Growth Factor on Invasiveness through the Extracellular Matrix in high-and Low-metastatic Clones of Murine sarcoma.
| Project/Area Number |
04454373
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Toyama Medical and Pharmaceutical University, Faculty of Medicine |
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Principal Investigator |
MATSUI Hisao Toyama Medical and Pharmaceutical University, Faculty of Medicine, Associated professor., 医学部, 助教授 (20173784)
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| Co-Investigator(Kenkyū-buntansha) |
KANAMORI Masahiko Toyama Medical and Pharmaceutical University, Faculty of Medicine, Assistant pro, 医学部, 助手 (20204547)
TSUJI Haruo Toyama Medical and Pharmaceutical University, Faculty of Medicine, Professor., 医学部, 教授 (90009449)
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| Project Period (FY) |
1992 – 1993
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| Keywords | tumor invasion / metastasis / murine sarcoma / extracellular matrix / epidermal growth factor / laminin / type IV collagen |
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| Research Abstract |
We investigated the invasiveness of tumor cells through the extracellular matrix and influential effects of epidermal growth factor (EGF) on tumor cell invasion using in vitro systems in high-[RCT(+)] and low-metastatic [RCT(-)] clones established from poorly differentiated murine RCT sarcoma in C3H/He mice. In the invasion assay, RCT(+) cells were more invasive than RCT(-) cells. The attachment of RCT(+) cells to extracellular matrix components and the degradation of type IV collagen by the cells were significantly greater than with RCT(-) cells. However, there was no significant difference in the migration of cells to the extracellular matrix components between cultured RCT(+) and RCT(-) cells. These findings suggested that the different invasiveness of these clone cells was associated with the difference in the ability of attachment and degradation of the matrix.
We investigated the correlation between serum levels of laminin and type IV collagen and pulmonary metastases in vivo, usi
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ng a murine sarcoma model of spontaneous pulmonary metastasis. The result showed that serum laminin and type IV collagen levels were found to be increased with the advance of metastasis formation. In the present study, our data provided evidence to suggest that elevated levels of laminin and type IV collagen detected in the sera might be caused by tumor cell invasion to the matrix during metastatic cascades.
EGF did not affect the invasiveness of RCT(-) cells. In RCT(+) celles, EGF stimulated the invasiveness through the matrigel, the attachment to extracellular matrix components and the degradation of type IV collagen, while the migration to the matrix was not influenced by EGF.These findings suggested that the stimulatory effect of EGF on invasion is related to the acceleration of cell adhesion and the degradative cascade of the extracellular matrix in this tumor. We observed that the high- and low-affinity EGF receptors were expressed in both RCT(+) and RCT(-) cells, and the level of EGF receptor expression in RCT(+) cells was significantly higher than that in RCT(-) cells. In RCT(+) cells, EGF-induced phosphorylation of EGF receptor and pulmonary metastasis were inhibited by anti-EGF receptor monoclonal antibody which could block EGF binding to the high-affinity EGF receptor These findings suggested that EGF receptor activation has a functional role in the metastatic property of RCT sarcoma cells. Less
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