Analysis of multicellular 3-D spheroids formation of tumor cells by neutrophils having tumor metastasis-modulating activity.
| Project/Area Number |
16590124
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
YUI Satoru Teikyo University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助教授 (40192413)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Metastasis / Neutrophil / Cathepsin G / E-cadherin / Cell aggregation |
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| Research Abstract |
In the course of tumor metastasis, dissemination of tumor cells from the tumor mass seems to be a critical step. It has been proposed that the aggregates of tumor cells are formed in situ, and the clumps spread through lymph nodes or the blood stream, and they form emboli in distant microvessels to form metastatic foci. However, the physiologic factors inducing homotypic aggregation of tumor cells have not been clarified.
It was found in this research that neutrophils produce the factors that induce the aggregation of MCF-7 human breast carcinoma cells. The experiments to identify the neutrophil factors revealed that neutrophil proteases, especially cathepsin G induced the formation of highly aggregated multicellular spheroids of MCF-7 cells. Induction of the multicellular spheroids was dependent on E-cadherin, since the induction of MCF-7 aggregation was inhibited by antibody for E-cadherin.
To clarify the mechanism of induction of tumor cell aggregation by cathepsin G, it was examined whether the activity is inhibited by chymostatin, an enzyme inhibitor. As the result, the aggregation-inducing activity of cathepsin G was not inhibited by the inhibitor, suggesting that cathepsin G exerts the effect via a novel enzymatic activity-independent mechanism.
The homotypic aggregation of the tumor cells is induced both by attenuation of the integrin-mediated adherence to the culture substrate and by relative enhancement of E-cadherin-mediated homotypic adherence. Since cathepsin G treatment of the tumor cells did not reduce the integrin expression of the MCF-7 cells, it was suggested that the factor induces the inactivation of integrin molecules through a signal transduction within the cells.
These results, therefore indicate that cathepsin G induced the tumor cell aggregates by a novel mechanism, which involves binding of cathepsin G to the cells, followed by a signal transduction to inactivate integrin molecules.
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Report
(3 results)
Research Products
(6 results)
