The receptor tyrosine kinase inhibitor SU11248 impedes endothelial cell migration, tubule formation, and blood vessel formation in vivo, but has little effect on existing tumor vessels
The receptor tyrosine kinase inhibitor SU11248 impedes endothelial cell migration, tubule formation, and blood vessel formation in vivo, but has little effect on existing tumor vessels
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DOI：
10.1007/s10456-004-3149-y
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发表时间：
2004-01-01
期刊：
影响因子：
9.8
通讯作者：
Geng, Luis
中科院分区：
文献类型：
--
作者：
Osusky, Katherine L.;Hallahan, Dennis E.;Geng, Luis
在临床试验中，抗血管生成剂在少数肿瘤中产生消退。但可有效防止复发。为了确定血管内皮生长因子（VEGF）受体是否是预防转移性疾病的分子靶点，我们使用了VEGF受体的非特异性抑制剂SU11248。这种受体酪氨酸激酶（RTK）抑制剂防止迁移的内皮细胞和显着衰减的毛细血管样小管形成的内皮细胞培养。类似地，该药剂防止肿瘤血管窗模型中的血管形成。在肿瘤血管窗模型中，VEGF RTK抑制对已建立的血管产生最小的影响，并且通过功率多普勒分析研究对血流的影响很小。确定这些药物是否能减弱转移的发展。从背部皮肤切除刘易斯肺癌肿瘤，并对用和不用SU 11248治疗的肺转移进行定量。RTK抑制剂减弱了后肢肿瘤切除后肺转移的形成。相反，这些药物不会引起原发灶的消退，但会减缓肿瘤生长的进展。这些研究结果表明，VEGF拮抗剂的最大作用可能是防止新血管的形成，在常规治疗期间和之后给予现有的肿瘤性疾病。
Antiangiogenic agents produce regression in few tumors in clinical trials. but are effective in preventing recurrences. To determine whether the vascular endothelial growth factor (VEGF) receptor is a molecular target to prevent metastatic disease, we utilized a non-specific inhibitor of the VEGF receptor, SU11248. This receptor tyrosine kinase (RTK) inhibitor prevented migration of endothelial cells and markedly attenuated capillary-like tubule formation in endothelial cells in culture. Similarly, this agent prevented blood vessel formation in the tumor vascular window model. VEGF RTK inhibition produced minimal effects on established blood vessels in the tumor vascular window model and little effect on blood flow studied by power Doppler analysis. To determine whether these agents attenuate the development of metastases. Lewis lung carcinoma tumors were resected from the dorsal skin and lung metastases were quantified with and without treatment with SU11248. The RTK inhibitor attenuated the formation of lung metastases following resection of the hind limb tumor. In contrast, these agents did not induce regression of primaries but slowed the progression of tumor growth. These findings suggest that the greatest role for VEGF antagonists may be to prevent the formation of new blood vessels, during and after conventional therapy is given to existing neoplastic disease.