Vascular endothelial growth factor receptor 3 is involved in tumor angiogenesis and growth
Vascular endothelial growth factor receptor 3 is involved in tumor angiogenesis and growth
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DOI：
10.1158/0008-5472.can-06-3567
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发表时间：
2007-01-15
期刊：
影响因子：
11.2
通讯作者：
Alitalo, Kari
中科院分区：
文献类型：
--
作者：
Laakkonen, Pirjo;Waltari, Marika;Alitalo, Kari
血管内皮生长因子受体3 （VEGFR-3）结合VEGF-C和VEGF-D，对淋巴血管的发育至关重要。过表达VEGFR-3配体的实验性肿瘤诱导淋巴管发芽和扩大，并表现出向区域淋巴结及其他部位转移的增强，而可溶性形式的。p VEGFR-3阻断受体信号传导抑制这些变化和转移。由于VEGFR-3对于胚胎早期血管发育也是必不可少的，并且在肿瘤血管生成中被上调，我们想要确定靶向干扰VEGFR-3配体结合受体的抗体是否可以抑制原发肿瘤的生长。我们的研究结果表明，抗体干扰VEGFR-3功能可以抑制免疫功能低下小鼠体内几种人类肿瘤异种移植物的生长。免疫组化分析显示，与对照抗体处理的肿瘤相比，抗VEGFR-3处理的肿瘤血管密度明显降低，缺氧坏死的肿瘤组织增加，表明阻断VEGFR-3通路抑制了这些肿瘤的血管生成。正如预期的那样，抗vegfr -3治疗的肿瘤也缺乏淋巴管。这些结果表明，VEGFR-3通路有助于肿瘤血管生成，有效抑制肿瘤进展可能需要抑制多个血管生成靶点。
Vascular endothelial growth factor receptor 3 (VEGFR-3) binds VEGF-C and VEGF-D and is essential for the development of the lymphatic vasculalure. Experimental tumors that overexpress VEGFR-3 ligands induce lymphatic vessel sprouting and enlargement and show enhanced metastasis to regional lymph nodes and beyond, whereas a soluble form of. p VEGFR-3 that blocks receptor signaling inhibits these changes and metastasis. Because VEGFR-3 is also essential for the early blood vessel development in embryos and is up-regulated in tumor angiogenesis, we wanted to determine if an antibody targeting the receptor that interferes with VEGFR-3 ligand binding can inhibit primary tumor growth. Our results show that antibody interference with VEGFR-3 function can inhibit the growth of several human tumor xenografts in immunocompromised mice. Immunohistochemical analysis showed that the blood vessel density of anti-VEGFR-3-treated tumors was significantly decreased and hypoxic and necrotic tumor tissue was increased when compared with tumors treated with control antibody, indicating that blocking of the VEGFR-3 pathway inhibits angiogenesis in these tumors. As expected, the anti-VEGFR-3-treated tumors also lacked lymphatic vessels. These results suggest that the VEGFR-3 pathway contributes to tumor angiogenesis and that effective inhibition of tumor progression may require the inhibition of multiple angiogenic targets.