Expression of Vascular Endothelial Growth Factor and Tumor Necrosis Factor-alpha in Angiogenesis Induced by Lipopolysaccharide and Thalidomide in CT26 Murine Colon Cancer of BALB/c Mouse.
- Author:
Dong Lak CHOI
1
;
Chang Ho CHO
;
Jin Sook JEONG
;
Sook Hee HONG
;
Ghil Suk YOON
Author Information
1. Department of Surgery, Catholic University of Daegu School of Medicine, Daegu, Korea.
- Publication Type:Original Article
- Keywords:
Angiogenesis;
Colorectal cancer;
Vascular endothelial growth factor;
Tumor necrosis factor-alpha
- MeSH:
Animals;
Blotting, Western;
Colon*;
Colonic Neoplasms*;
Colorectal Neoplasms;
Cytokines;
Mice*;
Microvessels;
Neoplasm Metastasis;
Thalidomide*;
Tumor Necrosis Factor-alpha*;
Vascular Endothelial Growth Factor A*
- From:Journal of the Korean Society of Coloproctology
2004;20(3):125-132
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: The growth, progression, and metastasis of malignant neoplasms are influenced by the environment of the tumor and by proliferation of the tumor itself. Angiogenesis of a malignant neoplasm is a very important environmental factor of tumor growth and metastasis. Also, it is a prognostic factor for malignant neoplasms. The mechanism of angiogenesis, such as the effects of cytokines and angiogenesis-promoting factors, is incompletely understood. METHODS: This study was designed to define the role of tumor necrosis factor-alpha (TNF-alpha) and the vascular endothelial growth factor (VEGF) in angiogenesis induced by lipopolysaccharide (LPS) and thalidomide (anticytokine drug) in CT26 murine colon cancer transplanted to BALB/c mice. RESULTS: The tumor size in the LPS-treated group (n=3, 2.1+/-0.26 cm) was larger than it was in the LPS thalidomide-treated group (n=4, 1.95+/-0.19 cm) and in the control group (n=3, 1.6+/-0.20 cm) (P<0.05). The microvessel density determined by CD31 immunostaining was lowest for the control group and highest for the LPS- treated group, but the differences were not statistically significant. An immunohistochemical study showed that the expressions of TNF-alpha (P<0.01) and VEGF (P<0.05) were higher in the experimental groups than they were in the control group. Also, the LPS thalidomide-treated group had lower expressions of TNF-alpha (P<0.01) and VEGF (P<0.05) than the LPS-treated group. Western blots revealed that the TNF-alpha and the VEGF levels semiquantitatively increased from the control group to the LPS thalidomide-treated group to the LPS-treated group. CONCLUSIONS: Our study revealed that low doses of LPS stimulated angiogenesis through increased expression of TNF-alpha and VEGF. Thalidomide decreased angiogenesis, probably through suppression of TNF-alpha with a decreased expression of VEGF. We conclude that TNF-alpha, suppressed by thalidomide, in the model of transplanted colon cancer may inhibit angiogenesis through coincident decrease in the expression of VEGF.
