2000 Fiscal Year Final Research Report Summary
Tumor promotion effect by IL-1β gene transfer : Analysis of cancer-stromal interaction.
| Project/Area Number |
11670563
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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 |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
SAIJO Yasuo Tohoku University, School of Medicine, Research Associate, 医学部・附属病院, 助手 (10270828)
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| Co-Investigator(Kenkyū-buntansha) |
TAZAWA Ryushi Tohoku University, School of Medicine, Research Associate, 加齢医学研究所, 助手 (70301041)
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| Project Period (FY) |
1999 – 2000
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| Keywords | lung cancer / gene thransfer / IL-1β / cancer-stromal interaction / HGF |
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| 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.
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[Publications] Yasuo Saijo, Xin Hong, Masashi Tanaka, Ryushi Tazawa, Shu Qin Liu, Kaoru Saijo, Tadao Ohno, Kaoru Koike, Kazuhiro Ohkuda, Ken Satoh, and Toshihiro Nukiwa: "Autologous high-killing cytotoxic T lymphocytes against human lung cancer are induced using IL-1β, IL-2, IL-4 and IL-6 : Possible involvement of dendritic cells."Clin Cancer Res.. 5. 1203-1209 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Takuji Suzuki, Yasuo Saijo, Masahito Ebina, Masahiro Yaekashiwa, Masayoshi Minegishi, Shigeru Tsuchiya, Tasuke Konno, Shuichi Ono, Yuji Matsumura, Shigefumi Fujimura, and Toshihiro Nukiwa: "Bilateral pneumothoraces with multiple bullae in a patient with bronchiolitis obliterans 10 years after allogeneic bone marrow transplantation."Bone Marrow Transplantation.. 23. 829-831 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] George Sato, Yasuo Saijo, Bine Uchiyama, Nobuko Kumano, Shun-ichi Sugawara, Shigefumi Fujimura, Masami Satoh, Motoyasu Sagawa, Kazuhiro Ohkuda, Kaoru Koike, Yuko Minami, Ken Satoh, and Toshihiro Nukiwa.: "Prognostic value of nucleolar protein p120 in patients with resected lung adenocarcinoma"J Clin Oncol. 17. 2721-2727
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[Publications] Saito J, Nakai Y, Saijo Y, Nukiwa T, Koinumaru S, Matsuura Y, Aso N, Yamane Y, Tsukamoto T, Sayama T, Nakabayashi T: "A phase II trial of oral UFT plus cisplatin (CDDP) in patients with non-small cell lung cancer (NSCLC)."Lung Cancer. 31. 285-293 (2001)
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「研究成果報告書概要(欧文)」より
