Signaling mechanism of tumor angiogenesis.

我们通过使用突变小鼠模型证明(1)血管内皮生长因子受体-2 （VEGFR-2）通过单个酪氨酸利用独特的信号传导；(2)VEGFR-1在体内主要通过激活VEGFR-1+骨髓源性细胞在肿瘤（包括脑肿瘤）的生长中发挥重要作用。此外，我们发现肿瘤对抗血管生成治疗的抵抗部分依赖于应激下的代谢转变。此外，我们还发现了内源性抗血管生成蛋白TSP1功能的新途径。

We demonstrated that (1) vascular endothelial growth factorreceptor-2 (VEGFR-2) utilizes unique signaling via a single tyrosine by using mutantmouse model, and (2) VEGFR-1 plays an important role in growth of tumors includingbrain tumor in vivo mostly via activation of VEGFR-1+ bone-marrow-derived cells.Furthermore, we showed that resistance of tumors against antiangiogenic therapy is partlydependent on a metabolic shift under stresses. In addition, we found new pathway for thefunction of endogenous antiangiogenic protein TSP1.