| Project/Area Number |
11670563
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
SAIJO Yasuo Tohoku University, School of Medicine, Research Associate, 医学部・附属病院, 助手 (10270828)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAZAWA Ryushi Tohoku University, School of Medicine, Research Associate, 加齢医学研究所, 助手 (70301041)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | lung cancer / gene thransfer / IL-1β / cancer-stromal interaction / HGF |
|---|
| Research Abstract |
Interleukin-1β (IL-1β) is a multifunctional and proinflamatory cytokine and affects nearly all cell type. In this study, we have constructed the retroviral vector expressing a hybrid gene of signal sequence and human IL-1β gene. Mouse Lewis lung carcinoma (LLC) cells were transduced with IL=1β gene (LLC/IL-1β). LLC/IL-1β accelerated tumor growth in mice despite of no change of growth property in vitro. Immunohistochemistry of CD31 in LLC/IL-1β tumor revealed hyper-neovascularization. LLC/IL-1β cells secreted larger amount of VEGF and MIP-2 whose one of main function is angigenesis. Moreover, LLC/IL-1β tumor contained over 4 times higher concentration of hepatocyte growth factor (HGF), although LLC/IL-1β cells itself did not secreted HGF in vitro. In situ hybridization of HGF mRNA demonstrated that stromal fibroblasts overexpressed HGF mRNA.An anti-angiogenic agent TNP-470 inhibited tumor growth of LLC/IL-1β cells. These results demonstrated that secreting IL-1β into tumor milieu induces several angiogenic factors from cancer and stromal cells and thus promotes tumor growth through neovascularization.
|
