Effects of vascular endothelial growth factor and E-selectin on angiogenesis in the murine metastatic RCT sarcoma.
The relationship between vascular endothelial growth factor (VEGF) and induction of angiogenesis in high-metastatic RCT(+) or low-metastatic RCT(-) clones of the poorly differentiated murine RCT sarcoma was investigated. The association with E-selectin in VEGF-induced angiogenesis was also evaluated. RCT(+) cells produced significantly larger amounts of VEGF than RCT(-) cells. In a tube formation assay with murine lung microvascular endothelial (MLE) cells, conditioned medium from RCT(+) cells showed a significantly greater effect on tube formation than that from RCT(-) cells. Induction of tube formation was suppressed by anti-mouse VEGF monoclonal antibody. Furthermore, anti-mouse E-selectin monoclonal antibody suppressed the tube formation induced by recombinant mouse VEGF. In a flow-cytometric analysis, the expression of E-selectin on MLE cells was upregulated after pretreatment with conditioned medium from RCT(+) and RCT(-) cells. Conditioned medium from RCT(+) cells induced a higher expression of E-selectin compared to medium from RCT(-) cells. Anti-VEGF monoclonal antibody prevented the upregulation of E-selectin by the RCT cell-conditioned medium. These findings suggest that E-selectin plays an important role in the angiogenesis induced by VEGF. VEGF derived from tumor cells may enhance angiogenesis by upregulating the expression of E-selectin on vascular endothelial cells.
Aoki
M
M
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Toyama, Japan. g7410001@ms.toyama-mpu.ac.jp
Kanamori
M
M
Yudoh
K
K
Ohmori
K
K
Yasuda
T
T
Kimura
T
T
D000818:Animals; D000906:Antibodies / Q000276:immunology; D017077:Culture Media, Conditioned; D019040:E-Selectin / Q000276:immunology / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008222:Lymphokines / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D012509:Sarcoma / Q000098:blood supply* / Q000556:secondary; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D017077:Culture Media, Conditioned; D019040:E-Selectin; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors