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.
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.
Hanyu
Aki
A
Division of Biochemistry, Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan.
Kojima
Kiyotsugu
K
Hatake
Kiyohiko
K
Nomura
Kimie
K
Murayama
Hironori
H
Ishikawa
Yuichi
Y
Miyata
Satoshi
S
Ushijima
Masaru
M
Matsuura
Masaaki
M
Ogata
Etsuro
E
Miyazawa
Keiji
K
Imamura
Takeshi
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply* / Q000473:pathology / Q000556:secondary / Q000628:therapy; D005453:Fluorescence; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D042461:Vascular Endothelial Growth Factor A