| 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. |
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Choi, Dong Lak , Cho, Chang Ho , Jeong, Jin Sook , Hong, Sook Hee , Yoon, Ghil Suk |
1Department of Surgery, Catholic University of Daegu School of Medicine, Daegu, Korea.
2Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, Korea. gsyoon@knu.ac.kr
3Department of Pathology, Dong-A University Medical College, Busan, Korea.
4Department of Pathology, Kyungpook National University Medical School, Daegu, Korea. |
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| 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. |
| Key Words:
Angiogenesis; Colorectal cancer; Vascular endothelial growth factor; Tumor necrosis factor-alpha |
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