Interleukin 6 Production and Tumor Proliferation in Lung Cancer.

• Project/Area Number: 14571256
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Chiba University
• Principal Investigator: IIZASA Toshihiko Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (10272303)
• Co-Investigator(Kenkyū-buntansha): OTSUJI Mizuto Chiba University, University Hospital, Assistant, 医学部附属病院, 助手 (50344982) ; SHIBUYA Kiyoshi Chiba University, University Hospital, Lecturer, 医学部附属病院, 講師 (20302565) ; FUJISAWA Takehiko Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80110328) ; IYODA Akira Chiba University, University Hospital, Assistant, 医学部附属病院, 助手 (10302548) ; 関根 康雄 千葉大学, 大学院・医学研究院, 助手 (70312957) ; 斎藤 幸雄 千葉大学, 大学院・医学研究院, 講師 (60261905)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000); Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
• Keywords: Non-Small Cell Lung Cancer / Interleukin 6 / Immunotherapy / Gene Therapy / Microarray

Research Abstract

Interleukin 6 (IL-6) facilitates the differentiation of B cells to immunoglobulin secreting cells and is reported to be a proliferative factor in some tumors. In this study, we examined IL-6 production in non-small cell carcinoma (NSCLC) and the proliferation of tumor cells following IL-6 treatment in vitro and in vivo. We analyzed the expression of IL-6 mRNA and protein in a series of 15 human lung cancer cell lines (4 adenocarcinomas, 5 squamous call carcinomas, 2 large cell carcinomas and 4 small cell carcinomas) by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). We established an IL-6 producing cell line (ABC-1 #IL-6) by transfecting a human IL-6 cDNA into a human IL-6 non-producing NSCLC cell line (ABC-1). These two cell lines were used to determine tumor cell proliferation both in vivo and in vitro in order to clarify the effect of IL-6 on tumor growth and metastasis. Athymic nude mice, SCID mice and BALB/c mice were subcuta neously inoculated with these two cell lines and body weight, tumor growth and tumor doubling time were measured. The presence of IL-6 and tumor infiltrating lymphocytes (TILs) within tumor tissues was examined by immunohistochemical staining. Results: Eight of 15 (53%) lung cancer cell lines expressed both IL-6 mRNA and protein. Tumor lesions of both cell lines developed in nude and SCID mice although no such lesions of either cell lines developed in BALB/c mice. The tumor doubling time in nude and SCID mice was 2.97+/-1.22 days and 2.45+/-1.32 days respectively in mice inoculated with the cell line ABC-1#IL-6. These doubling times were statistically significantly shorter than those evident in mice inoculated. with the control original ABC-1 cell line (nude : p=0.0337, SCID : p=0.0119, unpaired t-test). The rates of cell proliferation in vitro of the ABC-1#IL-6 and original ABC-1 cells lines were comparable (p=0.1441 / unpaired t-test). Immunohistochemical staining revealed strong IL-6 expression in tumors derived from the IL-6 producing cell line but not in tumors derived from the original ABC-1 cell line (both in nude and SCID mice). Conclusion: 53% of lung cancer cell lines produce IL-6 mRNA and protein. Although IL-6 itself does not influence tumor cell proliferation in vitro, an association between IL-6 expression and tumor proliferation was found in vivo in nude and SCID mice. An anti-IL-6 reagent could provide a novel therapeutic strategy in patients with IL-6-producing lung tumors.

Research Products

• [Publications] Yamaji H, Iizasa T, Koh E, Suzuki M, Otsuji M, Chang H, Motohashi S, Yokoi S, Hiroshima K, Tagawa M, Nakayama T, Fujisawa T.: "Correlation between Interleukin 6 Production and Tumor Proliferation in Non-Small Cell Lung Cancer."Cancer Immunol Immunother. (in press). (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iizasa T, Fujisawa T, Baba M, Saitoh Y, Sekine Y.: "Evaluation of issues for the new staging (1997) of lung cancer with resected cases of non-small cell lung cancer."Nippon Rinsho. 60 Suppl 5. 250-254 (2002)
  • Description: 「研究成果報告書概要(欧文)」より