2000 Fiscal Year Final Research Report Summary
Ribozyme mediated cleavage of cell-associated isoform of vascular endothelial growth factor (VEGF) inhibits liver metastasis of a pancreatic cancer cellline
| Project/Area Number |
11680825
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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 |
Laboratory animal science
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| Research Institution | Tokai University |
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Principal Investigator |
UEYAMA Yoshito Tokai University Schcol of Medicine Associate Professorr, 医学部, 助教授 (30072408)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Masato Tokai University School of Medicine Associate Professor, 医学部, 助教授 (00164335)
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| Project Period (FY) |
1999 – 2000
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| Keywords | ribozyme / vascular endothelial growth factor / pancreatic cancer / isoform / distant metastasis / cancer gene therapy model / angiogenesis |
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| Research Abstract |
Stromal angiogenesis is an important factor for progression of malignant neoplasms. we used hammerhead ribozymes against vascular endothelial growth factor (VEGF) gene transcripts to downregulate cell-associated VEGF189 isoform function in a pancreatic cancer cell line MIA-PaCa2. The b-actin promoter-driven ribozyme sequences were introduced into the cells by lipofection. We evaluated their effects on growth and neovascularisation of the cell lines. Metastatic potential was evaluated by the injection of transformants into the splenic pulp of nude mice. Anti-VEGF189 ribozyme specifically and efficiently cleaved the VEGF189 mRNA isoform but not other types of isoforms in vitro. MIA-Paca2 introduced with anti-VEGF189 ribozyme did not show any alteration of growth rate under tissue culture conditions compared to MIA-Paca2 introduced with disabled ribozyme. Production of tissue type plasminogen activator decreased in the human umblical vascular endothelial cells cocultured with the MIA-Paca2 cell line introduced with anti-VEGF189. When the transformants were subcutaneously transplanted, tumour volume of the ribozyme-introduced MIA-Paca2 xenografts was significantly smaller than that of disabled ribozyme-introduced cell line xenografts (P<0.01, Dunnett's test). No metastasis was apparent of the MIA-Paca2 introduced with anti-VEGF189, while disabled ribozyme transfected MIA-Paca2 show significant liver metastasis (P<0.05, Fisher's exact test). These results suggested that the VEGF189 mRNA plays an important role in growth and metastatic potential through alteration of angiogenic balance in cancer tissue.
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[Publications] Osada H., Tokunaga T., Hatanaka H., Kawakami T., Tsuchida T., Abe Y., Tsugu A., Kijima H., Yamazaki H., Shima K., i Osamura Y, Ueyama Y.and Nakamura M.: "Gene expression of angiogenesis related factors in glioma."International Journal of Oncology. 18. 305-309 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Oshika Y., Nakamura M., Tokunaga T., Ohnishi Y., Abe Y., Tsuchida T., Tomii Y., Kijima H., Yamazaki H., Ozeki Y., Tamaoki N., Ueyama Y.: "Ribozyme approach to downregulate vascular endothelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC)."Euroepan Journal of Cancer. 36. 2390-2396 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Tokunaga T., Tsuchida T., Kijima H., Okamoto K., Oshika Y., Sawa N., Ohnishi Y., Yamazaki H., Miura S., Ueyama Y., Nakamura M.: "Ribozyme mediated inactivation of mutant K-ras oncogene in a colon cancer cell line."British Journal of Cancer. 83(6). 833-839 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Hatanaka H., Abe Y., Kamiya T., Morino F., Nagata J., Tokunaga T., Oshika Y., Suemizu H., Kijima H., Tsuchida T., Yamazaki H., Inoue H., Nakamura M.and Ueyama Y.: "Clinical implications of interleukin (IL)-10 induced by non-small-cell lung cancer."Annals of Oncology. 11. 815-819 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Morino F., Tokunaga T., Tsuchida T., Handa A., Nagata J., Tomii Y, Kijima H., Yamazaki H., Watanabe N., Matsuzaki S, Ueyama Y., Nakamura M.: "Hammerhead ribozyme specifically inhibits vascular endothelial growth factor gene expression in a human hepatocellular carcinoma cell line."International Journal of Oncology. 17. 495-499 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Tsuchida T., Kijima H., Hori S., Oshika Y., Tokunaga T., Kawai K., Yamazaki H., Ueyama Y., Scanlon K.J., Tamaoki N., Nakamura M.: "Adenovirus-mediated anti-K-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma."Cancer Gene Therapy. 7(3). 373-383 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Lee Y H, Tokunaga T, Oshika Y, Suto R, Yanagisawa K, Tomisawa M, Fukuda H, Nakano H, Abe S, Tateishi A, Kijima H, Yamazaki H, Tamaoki N, Ueyama Y, Nakamura M.: "Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma."European Journal of Cancer.. 35(7). 1089-1093 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Okamoto K, Oshika Y, Fukushima Y, Yoshimura M, Ohnishi Y, Tokunaga T, Hashimoto T, Hatanaka H, Tomii, Y, Yoshida Y, Miura S, Tsuchida T, Kijima H, Yamazaki H, Nakamura M, Ueyama Y: "Inhibition of liver metastasis of colon cancer by in vivo administration of anti-vascular endothelial growth factor antibody."Oncology Reports.. 6. 553-556 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Tomisawa M, Tokunaga T, Oshika Y, Tsuchida T, Fukushima H, Sato H, Kijima H, Yamazaki H, Ueyama Y, Tamaoki N, Nakamura M.: "Expression pattern of vascular endothelial growth factor isoform is closely correlated with tumour stage and vascularization in renal cell carcinoma."European Journal of Cancr. 35(1). 133-137 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Tokunaga T, Nakamura M, Oshika Y, Abe Y, Ozeki Y, Fukushima Y, Hatanaka H, Sadahiro S, Kijima H, Tsuchida T, Yamazaki H, Tamaoki N, Ueyama Y.: "Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer."British Journal of Cancer.. 79(2). 354-359 (1999)
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