ETS transcription factors Etv2 and Fli1b are required for tumor angiogenesis.
ETS transcription factors Etv2 and Fli1b are required for tumor angiogenesis.
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DOI：
10.1007/s10456-017-9539-8
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发表时间：
2017-08
期刊：
影响因子：
9.8
通讯作者：
Sumanas S
中科院分区：
文献类型：
--
作者：
Baltrunaite K;Craig MP;Palencia Desai S;Chaturvedi P;Pandey RN;Hegde RS;Sumanas S
ETS 转录因子 ETV2 / Etsrp 作为多种脊椎动物胚胎血管发育的关键调节因子。然而，其在病理性血管发育中的作用此前尚未被研究过。为了分析其在肿瘤血管生成中的作用，我们利用斑马鱼异种移植模型。使用光转换 kdrl:NLS-KikGR 线，我们证明所有肿瘤血管通过血管生成机制起源于现有的胚胎脉管系统。小鼠 B16 黑色素瘤细胞的异种移植导致整个胚胎脉管系统中 ETS 转录因子 etv2 和 fli1b 表达显着增加。 etv2无效突变体在发育后期经历了胚胎血管生成的显着恢复，表现出对肿瘤血管生成的强烈抑制。我们利用高度特异性且经过充分验证的光活化吗啉来抑制胚胎血管发生完成后的 Etv2 功能。 Etv2 功能的诱导性抑制导致肿瘤血管生成显着减少并抑制肿瘤生长。此外，在fli1b突变体胚胎中诱导性抑制Etv2功能导致肿瘤血管生成和生长更明显减少，表明Etv2和Fli1b在肿瘤血管生成过程中具有部分冗余的需求。这些结果证明了肿瘤血管生成中对 Etv2 和 Fli1b 的需求，并表明抑制这些 ETS 因子可能提供一种抑制肿瘤血管生成和减少肿瘤生长的新策略。
ETS transcription factor ETV2 / Etsrp functions as a key regulator of embryonic vascular development in multiple vertebrates. However, its role in pathological vascular development has not been previously investigated. To analyze its role in tumor angiogenesis, we utilized a zebrafish xenotransplantation model. Using a photoconvertible kdrl:NLS-KikGR line we demonstrated that all tumor vessels originate from the existing embryonic vasculature by the mechanism of angiogenesis. Xenotransplantation of mouse B16 melanoma cells resulted in a significant increase in expression of the ETS transcription factors etv2 and fli1b expression throughout the embryonic vasculature. etv2 null mutants which undergo significant recovery of embryonic angiogenesis during later developmental stages displayed a strong inhibition of tumor angiogenesis. We utilized highly specific and fully validated photoactivatable morpholinos to inhibit Etv2 function after embryonic vasculogenesis has completed. Inducible inhibition of Etv2 function resulted in a significant reduction of tumor angiogenesis and inhibition of tumor growth. Furthermore, inducible inhibition of Etv2 function in fli1b mutant embryos resulted in even stronger reduction in tumor angiogenesis and growth, demonstrating that Etv2 and Fli1b have a partially redundant requirement during tumor angiogenesis. These results demonstrate the requirement for Etv2 and Fli1b in tumor angiogenesis and suggest that inhibition of these ETS factors may present a novel strategy to inhibit tumor angiogenesis and reduce tumor growth.
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胚胎血管发育中的 ETS 转录因子。
影响因子：
9.8
作者：
Craig MP;Sumanas S
通讯作者：
Sumanas S
影响因子：
14.8
作者：
Nicoli, Stefania;Presta, Marco
通讯作者：
Presta, Marco
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
影响因子：
2.7
作者：
Moore, John C.;Sheppard-Tindell, Sarah;Shestopalov, Ilya A.;Yamazoe, Sayumi;Chen, James K.;Lawson, Nathan D.
通讯作者：
Lawson, Nathan D.
影响因子：
2.6
作者：
Liu, F;Wen, ZL
通讯作者：
Wen, ZL