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.
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.
Goi
Takanori
T
Department of Surgery I, Fukui Medical University, 23-3 Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan. tgoi@fmsrsa.fukui-med.ac.jp
Fujioka
Masako
M
Satoh
Yoshiki
Y
Tabata
Shinsuke
S
Koneri
Kenji
K
Nagano
Hideki
H
Hirono
Yasuo
Y
Katayama
Kanji
K
Hirose
Kazuo
K
Yamaguchi
Akio
A
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004702:Endocrine Glands / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use*; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000235:genetics*
D043925:Angiogenesis Inducing Agents; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D040262:Receptors, Vascular Endothelial Growth Factor