| Project/Area Number |
10557093
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Hematology
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| Research Institution | Japanese Foundation for Cancer Research (2000)
Jichi Medical University (1998-1999) |
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Principal Investigator |
HATAKE Kiyohiko Japanese Foundation for Cancer Research, Div. of Clinical Chemotherapy, Cancer Chemotherapy Center. Cancer Institute. Associate Chief, 癌化学療法センター・臨床部, 副部長 (80192699)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Muneo Biochemical Research Laboratory, Morinaga Milk Industry Co., Ltd. Associate Member, 生物科学研究所, 主任研究員
冨塚 浩 (富塚 浩) 自治医科大学, 医学部, 講師 (00285785)
照井 康仁 自治医科大学, 医学部, 講師 (10285786)
大月 哲也 自治医科大学, 医学部, 講師 (60275691)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2000: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | apoptosis / endothelial IL-8 / aminopeptidase N / purging tumor cells / アポトーシス / 内皮細胞 / インターロイキン8 / 白血病 / 抗腫瘍効果 |
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| Research Abstract |
We purified three kinds of undiscovered factor that induces apoptosis in leukemic cells from HL-60 human myeloid leukemic cell-conditioned media. We identified the N-terminal amino acid sequences, and we demonstrated that one of our factors, endothelial interleukin-8 induced apoptosis in both leukemic and lymphoma cells. Monocyte-derived IL-8 did not induce apoptosis, and we demonstrated that N-terminal AVLPR peptide induced apoptosis. We demonstrated that both endothelial IL-8 and peptide AVLPR induced apoptosis and antitumor effect in leukemia-bearing mice in vivo. NB4, derived from acute promyelocytic leukemia, is a resistant cell line for endothelial IL-8-induced apoptosis. We observed that expression of CD13 antigen, that is an aminopeptidase N, is related to resistance for endothelial IL-8-induced apoptosis. Neutralizing antibody for CD13 inhibited aminopeptidase N activity, and aminopeptidase inhibitors reversed resistance for endothelial IL-8-induced apoptosis.
CD13 is one of the resistant mechanism for endothelial IL-8-induced apoptosis. Next, we demonstrated that b2-microglobulin induced apoptosis in leukemia and lymphoma cells. β2-microglobulin induced apoptosis via activation of caspase-3 and NF-kB pathway, Anti-HLA antibodies induced apoptosis in T cell leukemic cells that is different pathway from b2-microglobulin-induced pathway. We also demonstrated that complement factor Bb induced apoptosis via CD11c receptor in leukemia cells. We hope that our apoptosis-inducing factors will help purging tumor cells in peripheral blood collected samples in cancer patients.
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