2003 Fiscal Year Final Research Report Summary
Research for the prevention of tumor cell metastasis based on the establishment of artificial lymph node genesis
| Project/Area Number |
14570278
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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 |
Immunology
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| Research Institution | RIKEN (The Institute of Physical and Chemical Research) |
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Principal Investigator |
YOSHIDA Hisahiro RIKEN (The Institute of Physical and Chemical Research), Immune System Development Group, Senior scientist, 免疫系構築グループ, 上級研究員 (20281090)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Peripheral lymph nodes / chemokine / CXCL13 / IL7Ra+ cells / LT・・ / VCAM-1 / ICAM-1+ mesenchymal cells / TRAF6 / Long term culture |
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| Research Abstract |
We have found that murine peripheral lymph nodes (PLN) anlagen develop in multi steps listed below,
1.Local expression of chemokine CXCL13 at PLN anlagen,
2.Migration of IL-7Ra+ cells to those anlagen,
3.Stimulation of IL-7Ra+ cells by local specific cytokines and expression of lymphotoxin (LT) ab by IL-7Ra+ cells,
4.Differentiation of specific mesenchyme cells by LTab and expression of adhesion molecules and chemokines by mesenchymal cells,
5.Migration of various lineage leukocytes to PLN anlagen,
6.Development of micro-architecture of PLN anlagen, including endothelial cells development.
In accordance with these developmental scheme, we tried to culture the key player of PLN development, IL-7Ra+ cells (inducer cells), and VCAM-1+ICAM-1+ mesenchymal cells (organizer cells). Although we have succeeded to culture the former more than 10 weeks in in vitro condition, we failed to culture the latter cells longer than 2 weeks. Then we transferred those in vitro cultivated cells to the nude mouse subcutaneous region. However, the transferred cells did not induced artificial PLN tissue. As we have found that CXCL13 is a key molecule to keep the inducer cells to PLN anlagen, we are still trying to find out the best condition to keep them in in vivo with multiple molecules those participate in PLN organogenesis
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