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KMID : 0356720040200030125
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Journal of the Korean Society of Coloproctology
2004 Volume.20 No. 3 p.125 ~ p.132
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Expression of Vascular Endothelial Growth Factor and Tumor Necrosis Factor-α 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
Yun Kil-Suk
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Abstract
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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-α (TNF-α) 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-α (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-α (P＜0.01) and VEGF (P＜0.05) than the LPS-treated group. Western blots revealed that the TNF-α 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-α and VEGF. Thalidomide decreased angiogenesis, probably through suppression of TNF-α with a decreased expression of VEGF. We conclude that TNF-α, suppressed by thalidomide, in the model of transplanted colon cancer may inhibit angiogenesis through coincident decrease in the expression of VEGF. J Korean Soc Coloproctol 2004;20:125-132
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KEYWORD
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Angiogenesis, Colorectal cancer, Vascular endothelial growth factor, Tumor necrosis factor-α, VEGF, TNF-α
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