| Project/Area Number |
18590302
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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 |
Pathological medical chemistry
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| Research Institution | University of Miyazaki |
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Principal Investigator |
MORISHITA Kazuhiro University of Miyazaki, Faculty of Medicine, Professor (80260321)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | ATL / TSLC1 / cancer / IGSF4 / 成人T細胞白血病 / がん抑制遺伝子 / 接着因子 |
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| Research Abstract |
Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4+ T cells associated with human T-cell leukemia virus type I (HTLV-I) infection. We have previously demonstrated that acute-type ATL cells display high levels of ectopic TSLC1 mRNA expression. In the present study, we demonstrated the involvement of TSLC1 in tumor growth and organ-infiltration. TSLC1 on chromosome 11q23 has been identified in non-small cell lung cancer (NSCLC) to be a tumor suppressor. In contrast, TSLC1 has recently been found to be highly and ectopically expressed in acute-type ATL cells and most HTLV-1-infected T-cell lines. Since the role of overexpressed TSLC1 in the course of tumor growth and organ-infiltration of ATL cells remains to be fully elucidated, we investigated the direct involvement of TSLC1 in the growth and infiltration of leukemia cells using C57BL/6J and NOD-SCID/ γc null (NOG) mice. Murine EL4 T-lymphoma cells expressing TSLC1 shortened the survival time of C57BL/6J mice after intraperitoneal injection, and human ED-40515 (-) cell lines expressing TSLC1 (ED/TSLC1) inoculated under the skin of NOG mice were the most efficient in causing the formation of large tumors. Moreover, by intravenous injection of ED/TSLC1, aggressive growth and infiltration of ED/TSLC1 were observed in the liver and other organs of NOG mice. These results suggest that TSLC1 plays an important role in tumor growth and organ infiltration in vivo, and that TSLC1 could be a promising immunotherapeutic target for the development of an antibody-based therapy against ATL.
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