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首页> 外文期刊>Journal of dermatological science >Establishment of a novel experimental model of human angiosarcoma and a VEGF-targeting therapeutic experiment
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Establishment of a novel experimental model of human angiosarcoma and a VEGF-targeting therapeutic experiment

机译：人血管肉瘤新型实验模型的建立及靶向VEGF的治疗实验

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Background: Angiosarcoma is one of the most life-threatening neoplasms with strong resistance to conventional chemotherapy/radiotherapy; consequently, alternative therapeutic agents are urgently required. One factor in delaying the therapy development is the limitation of experimental models. Objective: We established a novel experimental angiosarcoma model. Methods: From surgically resected tissue, human AS cell line was established. Using xenograft of AS cell line, we performed therapeutic experiments with the anti-human VEGF Ab or the receptor tyrosine kinase inhibitor. Results: First we generated an angiosarcoma cell line, HAMON (human angiosarcoma, monoclonal), which expresses CD31 and produces tumors in immunodeficient mice. HAMON expresses VEGFR2 and that exogenous VEGF leads to HAMON proliferation in vitro. Anti-human VEGF Ab bevacizumab treatment failed to suppress HAMON proliferation in vitro and in vivo. Furthermore, the receptor tyrosine kinase inhibitor sunitinib did not suppress HAMON proliferation in vitro. Similarly, in in vivo therapeutic experiments, even high doses of sunitinib failed to inhibit tumor growth. Finally, we checked whether compensatory activation of VEGF signaling occurred after sunitinib addition. VEGF protein secretion, VEGF mRNA synthesis and VEGFR2 phosphorylation all were unaffected in HAMON after sunitinib treatment. Conclusion: A novel in vitro and in vivo experimental model of human angiosarcoma has been successfully established. With this model, we were able to perform therapeutic experiments. In addition, our angiosarcoma cell line, HAMON, is quite useful for identifying key molecules in angiosarcoma.
机译：背景：血管肉瘤是最致命的肿瘤之一，对常规化学疗法/放射疗法有很强的抵抗力。因此，迫切需要替代治疗剂。延迟疗法发展的一个因素是实验模型的局限性。目的：我们建立了一种新型的实验性血管肉瘤模型。方法：从手术切除的组织中建立人AS细胞系。使用异种移植的AS细胞系，我们用抗人VEGF Ab或受体酪氨酸激酶抑制剂进行了治疗实验。结果：首先，我们生成了血管肉瘤细胞系HAMON（人血管肉瘤，单克隆），它表达CD31并在免疫缺陷小鼠中产生肿瘤。 HAMON表达VEGFR2，而外源性VEGF导致HAMON在体外增殖。抗人VEGF Ab贝伐单抗治疗无法在体外和体内抑制HAMON增殖。此外，受体酪氨酸激酶抑制剂舒尼替尼在体外不能抑制HAMON增殖。同样，在体内治疗实验中，即使高剂量的舒尼替尼也不能抑制肿瘤的生长。最后，我们检查了舒尼替尼添加后是否发生了VEGF信号的代偿性激活。舒尼替尼治疗后HAMON中VEGF蛋白的分泌，VEGF mRNA的合成和VEGFR2的磷酸化均不受影响。结论：成功建立了新型的人血管肉瘤体内外实验模型。使用此模型，我们能够执行治疗性实验。此外，我们的血管肉瘤细胞系HAMON对于鉴定血管肉瘤中的关键分子非常有用。

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