Functional in vivo optical imaging of tumor angiogenesis, growth, and metastasis prevented by administration of anti-human VEGF antibody in xenograft model of human fibrosarcoma HT1080 cells |
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| Authors: | Aki Hanyu Kiyotsugu Kojima Kiyohiko Hatake Kimie Nomura Hironori Murayama Yuichi Ishikawa Satoshi Miyata Masaru Ushijima Masaaki Matsuura Etsuro Ogata Keiji Miyazawa Takeshi Imamura |
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| Institution: | Division of Biochemistry, the Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo;;Olympus Bio-Imaging Laboratory, the Cancer Chemotherapy Center of the JFCR, Tokyo;;Life Science Group, Micro-Imaging System Division, MIS Live Cell Imaging Business Department, Olympus Corporation, Tokyo;;Division of Chemotherapy, the Cancer Chemotherapy Center of the JFCR, Tokyo;;Division of Pathology, the Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo;;Division of Bioinformatics, Genome Center of the JFCR, Tokyo;;Genome Cancer Research, the Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo;;Cancer Institute Hospital of the JFCR, Tokyo;;Department of Biochemistry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan |
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| Abstract: | Angiogenesis plays a crucial role in cancer progression and metastasis. Thus, blocking tumor angiogenesis is potentially a universal approach to prevent tumor establishment and metastasis. In this study, we used in vivo and ex vivo fluorescence imaging to show that an antihuman vascular endothelial growth factor (VEGF) antibody represses angiogenesis and the growth of primary tumors of human fibrosarcoma HT1080 cells in implanted nude mice. Interestingly, administering the antihuman VEGF antibody reduced the development of new blood vessels and normalized pre-existing tumor vasculature in HT1080 cell tumors. In addition, antihuman VEGF antibody treatment decreased lung metastasis from the primary tumor, whereas it failed to block lung metastasis in a lung colonization experiment in which tumor cells were injected into the tail vein. These results suggest that VEGF produced by primary HT1080 cell tumors has a crucial effect on lung metastasis. The present study indicates that the in vivo fluorescent microscopy system will be useful to investigate the biology of angiogenesis and test the effectiveness of angiogenesis inhibitors. ( Cancer Sci 2009) |
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