Suppression of Ewing's sarcoma tumor growth, tumor vessel formation, and vasculogenesis following anti vascular endothelial growth factor receptor-2 therapy.

ZHOU Z, BOLONTRADE MF, REDDY K, DUAN X, GUAN H, YU L, HICKLIN DJ, KLEINERMAN ES.

CLINICAL CANCER RESEARCH

AMER ASSOC CANCER RESEARCH

Lugar: Philadelphia, Pennsylvania; Año: 2007 vol. 13 p. 4867 - 4873

1078-0432

PURPOSE: We previously showed that bone marrow cells participate in new tumor vessel formation in Ewing´s sarcoma, and that vascular endothelial growth factor 165 (VEGF(165)) is critical to this process. The purpose of this study was to determine whether blocking VEGF receptor 2 (VEGFR-2) with DC101 antibody suppresses tumor growth, reduces tumor vessel formation, and inhibits the migration of bone marrow cells into the tumor. EXPERIMENTAL DESIGN: An H-2 MHC-mismatched bone marrow transplant Ewing´s sarcoma mouse model was used. Bone marrow cells from CB6F1 (MHC H-2(b/d)) mice were injected into irradiated BALB/cAnN mice (MHC H-2(d)). TC71 Ewing´s sarcoma cells were s.c. injected 4 weeks after the bone marrow transplantation. Mice were then treated i.p. with DC101 antibody or immunoglobulin G (control) twice a week for 3 weeks starting 3 days after tumor cell injection. RESULTS: DC101 antibody therapy significantly reduced tumor growth and tumor mean vessel density (P < 0.05) and increased tumor cell apoptosis. Decreased bone marrow cell migration into the tumor was also shown after DC101 therapy as assessed by the colocalization of H-2K(b) and CD31 using immunohistochemistry. DC101 inhibited the migration of both human and mouse vessel endothelial cells in vitro. CONCLUSION: These results indicated that blocking VEGFR-2 with DC101 antibodies may be a useful therapeutic approach for treating patients with Ewing´s sarcoma.