已有研究证实B7-H3在肾癌血管组织特异表达，且与临床预后密切相关，但其在肿瘤血管形成中是否存在作用尚不清楚。髓系细胞TEM（Tie-2 expressing monocytes）通过分泌促血管生长因子、分化为内皮细胞或提供物理支撑的周细胞，在肿瘤新生血管形成中发挥关键作用，但确切分子机制仍待阐明。最近，本课题组发现肿瘤浸润TEM异常高表达B7-H3，且前期工作还发现该分子可促进细胞粘附、单核巨噬细胞分泌炎性细胞因子以及干细胞诱导分化。因此我们推测B7-H3参与了TEM介导的肿瘤新生血管形成。鉴此，本项目拟开展下列研究：1）从形态学及细胞水平分析B7-H3+细胞在肿瘤血管中的精确定位、来源以及TEM上B7-H3的表达与微血管密度的关系和表达调控机制；2）从TEM促血管形成的三种方式入手，通过体内外实验，从分子、细胞以及整体水平分析B7-H3在TEM介导的肿瘤血管形成中的作用及分子机制。

Tumor-induced angiogenesis is crucial for tumor growth and metastasis. Previous studies showed that B7-H3 is significantly expressed by tumor vascular endothelial cells, and prognosticates a poor clinical outcome of renal carcinoma. However, the role of B7-H3 on tumor-induced angiogenesis remains unknown. Our recent studies indicated that B7-H3 is expressed by Tie-2 expressing monocytes (TEM), a population of Myeloid-derived cells, induced by tumor environment. TEM plays an important role in tumor vessel formation through differentiation into vascular endothelial cells (ECs),secration of bFGF and VEGF to support ECs growth or as pericyte progenitors to provide base membrane for ECs adhesion. In our previous work, we found that B7-H3 is important in adhesion between cell and cellular matrix, secreation of ctyokines such as TNF-α and promotion of cell differentiation in vitro. According to our findings and previous reports, we hypothesize that B7-H3 plays a critical role in promoting tumor vessel formation mediated by TEM. To test this hypothesis, this project will to confirm the location of B7-H3+population on tumor vessel tissues and analyze the contribution proportion of TEM on the expression of B7-H3; to assess the correlation between B7-H3 levels on TEM and intratumoral microvessel density; to investigate the effect and biofunctional mechanism of B7-H3 on tumor vessel formation mediated by TEM in vitro and in vivi. This project aims to analyze the effect and mechanism of B7-H3 on tumor-induced angiogenesis mediated by TEM in renal carcinoma.