Abstract VEGF/VEGFR signaling is essential for pathological angiogenesis. It has been reported that Flt-1 (VEGFR-1) is expressed not only in vascular endothelial cells but also in monocyte/macrophages. Previously, we and others reported that bone marrow derived cells which expressed Flt-1 were involved in the formation of pre-metastatic niche in mouse tumor model. However, the role of Flt-1 signal in tumorigenesis is not fully understood. To clarify the involvement of Flt-1 in solid tumor growth, we used wild type (Wt) mice and Flt-1 tyrosine kinase-deficient (Flt-1 TK-/-) mice which developed basically normal blood vessels and survived. In allograft cancer model, tumor growth was significantly slower in Flt-1 TK-/- mice compared with that in Wt mice. Survival rate of Flt-1 TK-/- mice were also higher than Wt mice under tumor-bearing condition. The degree of tumor angiogenesis and infiltration of macrophage-lineage cells in tumor tissues were remarkably suppressed in Flt-1 TK-/- mice compared with those in Wt mice. Surprisingly, endothelial cells and macrophage-lineage cells at the surrounding tissue of tumors were similar in both mice. The number of pericyte marker-positive cells covered with vascular endothelial cells was reduced in tumor tissue in Flt-1 TK-/- mice compared with that in Wt mice. To distinguish which Flt-1 signal on the vascular endothelial cell or on the macrophage is important, we performed bone marrow transplantation. Tumor volume in Wt mice implanted with bone marrow derived from Flt-1 TK-/- mice was significantly smaller than that in Wt mice implanted with bone marrow derived from Wt mice. In tumor tissue inoculated in Wt mice implanted with Flt-1 TK-/- bone marrow, angiogenesis and infiltration of macrophage-lineage cells were significantly decreased compared with Wt mice implanted with Wt bone marrow. Based on these results, we suggest that, in some tumors, Flt-1 signaling is important for bone marrow-derived macrophage-migration into tumors which promotes tumor angiogenesis and tumor growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1301.