The influence of tumour resection on angiostatin levels and tumour growth--an experimental study in tumour-bearing mice.
The phenomenon of primary neoplasms inhibiting the growth of their metastatic lesions is thought to be related to endogenous angiogenesis inhibitors. The aim of this experiment was to investigate the influence of tumour resection on angiostatin levels and tumour growth using a tumour-bearing mouse model. A primary Lewis lung cancer tumour model was established in C57BL/6 mice and these mice were divided into two groups 10 days after the tumour cells were inoculated. In the surgical resection group (S group) the tumour was resected, but in the control group (C group) a sham operation was performed. The level of angiostatin in the sera was analysed 5 days after the operation by western blotting. To observe tumour growth, four Lewis lung cancer models were established in these mice from both the S and C groups. An immunohistochemical analysis of the tumour tissues was conducted to estimate the proliferation and apoptotic rates of the tumour cells, as well as the amount of neoangiogenesis in the tumours. Angiostatin was observed in the tumour-bearing mice, but disappeared within 5 days after the tumour had been resected. Increased tumour growth was observed in all of the tumour models in the S group compared with the C group and the differences were significant. A significantly higher intratumour vessel density and proliferation cell index, but a significantly lower apoptotic index were also found in the S group compared with the C group. These findings demonstrated that angiostatin was generated directly from the tumour tissue. Furthermore, tumour resection accelerates the growth of other tumours and this is probably related to multiple factors including increased neoangiogenesis, increased tumour cell proliferation, and decreased apoptosis.
Li
T S
TS
First Department of Surgery, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, Japan 755-8505. litaoshe@po.cc.yamaguchi-u.ac.jp
Kaneda
Y
Y
Ueda
K
K
Hamano
K
K
Zempo
N
N
Esato
K
K
D043168:Angiostatins; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000097:blood* / Q000098:blood supply / Q000601:surgery*; D002455:Cell Division; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000097:blood*; D009368:Neoplasm Transplantation / Q000379:methods; D009389:Neovascularization, Pathologic / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood*; D010958:Plasminogen; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D010446:Peptide Fragments; D043168:Angiostatins; D010958:Plasminogen