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Suppression of pulmonary metastasis by angiogenesis inhibitor TNP‐470 in murine osteosarcoma
Author(s) -
Mori Shigeki,
Ueda Takafumi,
Kuratsu Shigeyuki,
Hosono Noboru,
Izawa Kazutaka,
Uchida Atsumasa
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910610125
Subject(s) - osteosarcoma , angiogenesis , metastasis , immunohistochemistry , in vivo , lung , angiogenesis inhibitor , pathology , cancer research , medicine , cancer , biology , microbiology and biotechnology
We treated a murine osteosarcoma cell line, LM8, which preferentially metastasizes to the lungs, with a new angiogenesis inhibitor, TNP‐470, to evaluate the efficacy of this compound in the suppression of pulmonary metastasis of osteosarcoma. In an in vivo experiment, tumor cells were inoculated i.v. into C3H mice, and TNP‐470 or vehicle alone (control group) was administered s.c. every day for 3 weeks. In the TNP‐470‐treated groups, both the number of pulmonary metastatic nodules and the lung wet weight were significantly reduced in a dose‐dependent manner. Similarly, vascular density in the metastatic tumors estimated by immunohistochemical staining with anti‐von‐Willebrand factor antibody as an endothelial marker were significantly reduced. No severe side‐effects were found. In an in vitro experiment, viable tumor cells were counted after 3 days' treatment with TNP‐470. The 50% inhibitory concentration was 0.6 ng/ml for LM8, which was more sensitive than other tumor cells previously reported. Our results show that TNP‐470 suppresses the pulmonary metastasis of LM8 and suggest that both its anti‐angiogenic activity and cytostatic activity towards LM8 are responsible for the anti‐tumor effect. © 1995 Wiley‐Liss, Inc .