Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis.
Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis.
复制标题
血管内皮生长因子受体 3 参与肿瘤血管生成过程中内皮细胞衬里完整性的维持。
作者：
Hajime Kubo;Takashi Fujiwara;L. Jussila;H. Hashi;M. Ogawa;Kenji Shimizu;Masaaki Awane;Y. Sakai;Arimichi Takabayashi;Kari Alitalo;Yoshio Yamaoka;Shin
血管内皮生长因子（VEGF）在肿瘤血管生成中起主要作用。然而，VEGF-C被认为刺激淋巴管的生长，因为其特异性受体VEGF受体-3（VEGFR-3）的表达被证明限于淋巴管。在这里，我们证明了一种新的阻断性单克隆抗体（mAb）对VEGFR-3的失活通过抑制肿瘤组织的新血管生成来抑制肿瘤生长。尽管VEGFR-3在成人血管中不表达，但其在荷瘤组织的血管内皮细胞中被诱导。因此，VEGFR-3是另一种参与肿瘤诱导的血管生成的受体酪氨酸激酶。肿瘤组织中的微出血是AFL 4 mAb处理小鼠特异性的最显著的组织学发现。扫描显微镜检查显示毛细血管后微静脉的内皮衬里破裂，这可能是微出血和随后近端血管塌陷的原因。这些发现表明VEGFR-3参与维持血管生成过程中内皮衬里的完整性。此外，我们的研究结果表明，VEGF-C/VEGFR-3通路可能成为癌症治疗的另一个候选靶点。（血。2000;96：546-553）
Vascular endothelial growth factor (VEGF) plays a major role in tumor angiogenesis. VEGF-C, however, is thought to stimulate the growth of lymphatic vessels because an expression of its specific receptor, VEGF receptor-3 (VEGFR-3), was demonstrated to be restricted to lymphatic vessels. Here we demonstrate that the inactivation of VEGFR-3 by a novel blocking monoclonal antibody (mAb) suppresses tumor growth by inhibiting the neo-angiogenesis of tumor-bearing tissues. Although VEGFR-3 is not expressed in adult blood vessels, it is induced in vascular endothelial cells of the tumor-bearing tissues. Hence, VEGFR-3 is another receptor tyrosine kinase involved in tumor-induced angiogenesis. Micro-hemorrhage in the tumor-bearing tissue was the most conspicuous histologic finding specific to AFL4 mAb-treated mice. Scanning microscopy demonstrated disruptions of the endothelial lining of the postcapillary venule, probably the cause of micro-hemorrhage and the subsequent collapse of the proximal vessels. These findings suggest the involvement of VEGFR-3 in maintaining the integrity of the endothelial lining during angiogenesis. Moreover, our results suggest that the VEGF-C/VEGFR-3 pathway may serve another candidate target for cancer therapy. (Blood. 2000;96:546-553)
影响因子：
2.7
作者：
Oh, SJ;Jeltsch, MM;Wilting, J
通讯作者：
Wilting, J
影响因子：
15.9
作者：
Lin, PN;Polverini, P;Peters, K
通讯作者：
Peters, K