| Project/Area Number |
16390120
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | JUNTENDO UNIVERSITY |
|---|
Principal Investigator |
OKUMURA Ko Juntendo University, Immunology, Professor, 医学部, 教授 (50009700)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAGITA Hideo Juntendo University, Immunology, Associate Professor, 医学部, 助教授 (30182306)
TAKEDA Kazuyoshi Juntendo University, Immunology, Assistant Professor, 医学部, 講師 (80272821)
NAKANO Hiroyasu Juntendo University, Immunology, Assistant Professor, 医学部, 講師 (70276476)
EBATA Tomohiko Juntendo University, Immunology, Research associate, 医学部, 助手 (30343487)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2005: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2004: ¥7,000,000 (Direct Cost: ¥7,000,000)
|
|---|
| Keywords | TWEAK / Fn14 / tumor / apoptosis / cytokine / angiogenesis / tumor rejection / IκBα / IL-8 / GM-CSF / RANTES / 炎症 |
|---|
| Research Abstract |
TWEAK and its receptor, Fn14 belong to the tumor necrosis factor (TNF) superfamily and the TNF receptor superfamily, respectively. We have previously shown that TWEAK induces production of pro-inflammatory chemokine, cell migration, proliferation, and cell death through Fn14. To investigate roles for TWEAK/Fn14 interaction in tumor-associated angiogenesis and tumor rejection by macrophages, we generated anti-murine TWEAK monoclonal antibody (mAb), and transfectants expressing TWEAK or Fn14. We examined the effect of TWEAK or Fn14 expression in tumor cells on tumor outgrowth in vivo. Administration of neutralizing anti-TWEAK mAb significantly reduced the frequency of tumor rejection and shortened the survival of mice intraperitoneally inoculated with TWEAK-sensitive Fn14-expressing tumor cells. Moreover, anti-TWEAK mAb treatment promoted the subcutaneous growth of TWEAK-sensitive Fn14-expressing tumor cells, and this promotion was abolished by the inhibition of macrophage infiltration but not NK cell depletion. In contrast, administration of anti-TWEAK mAb had no apparent effect on the growth of TWEAK-resistant tumor cells, even if tumor cells expressed Fn14. These results indicate that TWEAK mediates anti-tumor effect of macrophages in vivo. Taken that TWEAK expression in tumor cells had no significant effect on subcutaneous tumor growth, TWEAK/Fn14 interaction does not appear to promote tumor growth through enhancing angiogenesis.
|
