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Suppression of tumor growth by intra-muscular transfer of naked DNA encoding adrenomedullin antagonist

Cancer Gene Therapy volume 14, pages 39–44 (2007)Cite this article

Abstract

We have recently reported that the intra-tumoral injection of adrenomedullin (AM) antagonist (AMA; AM (22–52)) peptides significantly reduced the in vivo growth of a pancreatic cancer cell line in severely combined immunodeficient (SCID) mice. In the present study, we examined the effects of intra-tumoral and intra-muscular transfers of naked DNA encoding AMA on the in vivo growth of cancer cell lines. We demonstrate that these treatments induce the regression of a pancreatic cancer cell line and a breast cancer cell line inoculated in SCID mice. Furthermore, CD31-positive cells disappear completely from tumor tissues, following treatment, indicating that neo-vascularization is entirely inhibited. These results suggest that the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA might be a promising alternative modality for treating human cancers.

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References

  1. Ishikawa T, Chen J, Wang J, Okada F, Sugiyama T, Kobayashi T et al. Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by suppressing angiogenesis. Oncogene 2003; 22: 1238–1242.

    Article  CAS  Google Scholar 

  2. Iimuro S, Shindo T, Moriyama N, Amaki T, Niu P, Takeda N et al. Angiogenic effects of adrenomedullin in ischemia and tumor growth. Circ Res 2004; 95: 415–423.

    Article  CAS  Google Scholar 

  3. Tokunaga N, Nagaya N, Shirai M, Tanaka E, Ishibashi-Ueda H, Harada-Shiba M et al. Adrenomedullin gene transfer induces therapeutic angiogenesis in a rabbit model of chronic hind limb ischemia: benefits of a novel nonviral vector, gelatin. Circulation 2004; 109: 526–531.

    Article  CAS  Google Scholar 

  4. Niidome T, Huang L . Gene therapy progress and prospects: nonviral vectors. Gene Therapy 2002; 9: 1647–1652.

    Article  CAS  Google Scholar 

  5. Lu QL, Bou-Gharios G, Partridge TA . Non-viral gene delivery in skeletal muscle: a protein factory. Gene Therapy 2003; 10: 131–142.

    Article  CAS  Google Scholar 

  6. Herweijer H, Wolff JA . Progress and prospects: naked DNA gene transfer and therapy. Gene Therapy 2003; 10: 453–458.

    Article  CAS  Google Scholar 

  7. Feldman AL, Libutti SK . Progress in antiangiogenic gene therapy of cancer. Cancer 2000; 89: 1181–1194.

    Article  CAS  Google Scholar 

  8. Blezinger P, Wang J, Gondo M, Quezada A, Mehrens D, French M et al. Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene. Nat Biotechnol 1999; 17: 343–348.

    Article  CAS  Google Scholar 

  9. Unger EC, Hersh E, Vannan M, McCreery T . Gene delivery using ultrasound contrast agents. Echocardiography 2001; 18: 355–3361.

    Article  CAS  Google Scholar 

  10. Culmsee C, Monnig J, Kemp BE, Mattson MP . AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. J Mol Neurosci 2001; 17: 45–58.

    Article  CAS  Google Scholar 

  11. Yun H, Lee M, Kim SS, Ha J . Glucose deprivation increases mRNA stability of vascular endothelial growth factor through activation of AMP-activated protein kinase in DU145 prostate carcinoma. J Biol Chem 2005; 280: 9963–9972.

    Article  CAS  Google Scholar 

  12. Di Marco S, Mazroui R, Dallaire P, Chittur S, Tenenbaum SA, Radzioch D et al. NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release. Mol Cell Biol 2005; 25: 6533–6545.

    Article  CAS  Google Scholar 

  13. Kong H-L, Crystal RG . Gene therapy strategies for tumor antiangiogenesis. J Natl Cancer Inst 1998; 90: 273–286.

    Article  CAS  Google Scholar 

  14. Taniyama Y, Tachibana K, Hiraoka K, Aoki M, Yamamoto S, Matsumoto K et al. Development of safe and efficient novel nonviral gene transfer using ultrasound: enhancement of transfection efficiency of naked plasmid DNA in skeletal muscle. Gene Therapy 2002; 9: 372–380.

    Article  CAS  Google Scholar 

  15. Taniyama Y, Tachibana K, Hiraoka K, Namba T, Yamasaki K, Hashiya N et al. Local delivery of plasmid DNA into rat carotid artery using ultrasound. Circulation 2002; 105: 1233–1239.

    Article  CAS  Google Scholar 

  16. Endoh M, Koibuchi N, Sato M, Morishita R, Kanzaki T, Murata Y et al. Fetal gene transfer by intrauterine injection with microbubble-enhanced ultrasound. Mol Ther 2002; 5: 501–508.

    Article  CAS  Google Scholar 

  17. Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H et al. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun 1993; 192: 553–560.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Dr Jun-ichi Hamada (Division of Cancer Related genes, Institute for Genetic Medicine) and Dr Hiroshi Ishikura (The First Department of Pathology, Hokkaido University School of Medicine) for providing us with the cell lines. We thank Ms M Yanome for her assistance in preparing the manuscript. This work was supported in part by Grants-in-Aid for Cancer Research from the Japanese Ministry of Education, Culture, Sports and Science.

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Author notes

  1. J Hamuro

    Present address: Department of Biomolecular Function, Yamagata Graduate School of Medical Science, Yamagata, Japan

Authors and Affiliations

  1. Division of Cancer Biology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan

    T Miseki, H Kawakami, M Natsuizaka, S Darmanin, H Y Cui, J Chen, Q Fu, F Okada & M Kobayashi

  2. Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan

    T Miseki, H Kawakami, M Natsuizaka, S Darmanin, H Y Cui & M Asaka

  3. Division of Cancer-related Genes, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan

    J Chen

  4. Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University, Yamagata, Japan

    F Okada

  5. Department of Oral Pathobiological Science, Hokkaido University Graduate Dental School, Hokkaido, Japan

    M Shindo, F Higashino & M Kobayashi

  6. Oncorex Inc., Sapparo, Hokkaido, Japan

    J Hamuro

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  1. T Miseki
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  7. Q Fu
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  8. F Okada
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  11. M Asaka
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Corresponding author

Correspondence to M Kobayashi.

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Miseki, T., Kawakami, H., Natsuizaka, M. et al. Suppression of tumor growth by intra-muscular transfer of naked DNA encoding adrenomedullin antagonist. Cancer Gene Ther 14, 39–44 (2007). https://doi.org/10.1038/sj.cgt.7700979

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  • DOI: https://doi.org/10.1038/sj.cgt.7700979

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