Angiogenesis and tumor proliferation/metastasis of human colorectal cancer cell line SW620 transfected with endocrine glands-derived-vascular endothelial growth factor, as a new angiogenic factor.

Takanori Goi,Kazuo Hirose,Hideki Nagano,Yoshiki Satoh,Masako Fujioka,Kanji Katayama,Akio Yamaguchi,Shinsuke Tabata,Kenji Koneri,Yasuo Hirono

doi:10.1158/0008-5472.can-3696-2

Takanori Goi, Kazuo Hirose + Show 8 more

Open Access

https://doi.org/10.1158/0008-5472.can-3696-2

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Journal: Cancer research	Publication Date: Mar 15, 2004
Citations: 69	License type: cc-by

Affiliation: University of Fukui

Abstract

Endocrine glands-derived-vascular endothelial growth factor (EG-VEGF) was recently cloned as a new angiogenic factor that selectively acts on the endothelium of endocrine gland cells. We evaluated the involvement of EG-VEGF in colorectal cancer. The expression of EG-VEGF was confirmed in all of the colorectal cancer cell lines. (On the other hand, the expression of EG-VEGF mRNA was not detected in colorectal normal mucosae.) Stable EG-VEGF infectors of colorectal cancer cell line SW620 were produced, EG-VEGF transfectants were implanted into cecum and s.c., and cell proliferation was evaluated. Angiogenesis was evaluated by dorsal air sac method. Liver metastasis was evaluated after the implantation of EG-VEGF transfectants into the mouse spleen. Tumor proliferation (cecum, s.c.) was significantly higher in the EG-VEGF transfectants than in the control cells. The small vessels were significantly increased in EG-VEGF transfectants as compared with those in control cells. Also, liver metastatic ratio was higher in the EG-VEGF transfectants than in the control cells. In this study, EG-VEGF, a new angiogenic factor, may lead to angiogenesis, promoting cell proliferation and liver metastasis in colorectal cancers. When the EG-VEGF gene-overexpressing colorectal cancer cell line that had been treated with phosphorothioate antisense EG-VEGF oligonucleotides was injected s.c. into mice, angiogenesis and tumor growth were inhibited. Although the novel angiogenesis factor EG-VEGF was not expressed in the normal colorectal mucosa, it was expressed in colorectal cancer cells, which indicates that it is a cancer-specific and possibly tissue-specific angiogenesis factor in the large intestine, and which suggests that it can be targeted by a novel antiangiogenesis therapy.

Highlights

Hematogenous metastasis occurs by the following processes: (a) cell proliferation and angiogenesis in the primary lesion; (b) infiltration to surrounding areas; (c) vascular invasion; (d) adhesion to vascular endothelial cells in the target organ; (e) extravascular escape and migration; and (f) proliferation and angiogenesis in metastatic lesions [1]
In the blood vessels of normal tissue, angiogenesis is maintained by the action of angiogenesis inhibitory factors, such as IFN and NK4/malignostatin [3, 4], that regulate the action of its promoting factors such as vascular endothelial growth factor, b-fibroblast growth factor, hepatocyte growth factor, and interleukin-8 [5, 6]
Tumor proliferation was significantly higher in endocrine glands-derivedvascular endothelial growth factor (EG-vascular endothelial growth factor (VEGF)) transfectant SW620 than in empty-vector transfectant SW620

Summary

Introduction

Hematogenous metastasis occurs by the following processes: (a) cell proliferation and angiogenesis in the primary lesion; (b) infiltration to surrounding areas; (c) vascular invasion; (d) adhesion to vascular endothelial cells in the target organ; (e) extravascular escape and migration; and (f) proliferation and angiogenesis in metastatic lesions [1]. In processes a and f, angiogenesis is controlled by the balance between its promoting and inhibiting factors [2]. In the blood vessels of normal tissue, angiogenesis is maintained by the action of angiogenesis inhibitory factors, such as IFN and NK4/malignostatin [3, 4], that regulate the action of its promoting factors such as vascular endothelial growth factor, b-fibroblast growth factor, hepatocyte growth factor, and interleukin-8 [5, 6]. Tumor proliferation and metastasis to antiangiogenesis therapy in which tumor proliferation is inhibited by inhibiting the formation of new tumor vessels using angiogenesis inhibitory factors and drugs (8 –11)

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