OVA66 promotes tumour angiogenesis and progression through enhancing autocrine VEGF-VEGFR2 signalling
OVA66 promotes tumour angiogenesis and progression through enhancing autocrine VEGF-VEGFR2 signalling
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OVA66 通过增强自分泌 VEGF-VEGFR2 信号传导促进肿瘤血管生成和进展
DOI：
10.1016/j.ebiom.2019.02.051
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发表时间：
2019-03-01
期刊：
影响因子：
11.1
通讯作者：
Wei, Qing
中科院分区：
文献类型：
--
作者：
Song, Feifei;Chen, Qi;Wei, Qing
背景资料：肿瘤细胞中自分泌VEGF-VEGFR 2信号传导的激活激活了细胞增殖、存活和血管生成，所有这些对于肿瘤进展都是至关重要的。卵巢癌相关抗原66（OVA 66）是现在已知的过度表达在多种肿瘤中发挥作用，在肿瘤的发展，但潜在的机制还没有得到充分investigated.Methods：我们采用卵巢癌和宫颈癌细胞和小鼠模型来检测OVA 66的作用，在血管生成，生长和转移的癌细胞。免疫荧光和western blot检测OVA 66对自分泌VEGF-VEGFR 2信号通路的调节作用。采用免疫组织化学和生物信息学分析方法检测OVA 66与VEGF表达的相关性。结果：OVA 66在癌细胞系中过表达促进了体外和体内VEGF的分泌、肿瘤生长和血管生成。相反，shRNA介导的OVA 66敲低具有相反的效果。从机制上讲，OVA 66过表达被发现可以促进肿瘤细胞中的自分泌VEGF-VEGFR 2正反馈信号环，导致VEGF对肿瘤血管生成和增殖的放大作用，并分别在体外和体内增加迁移。最后，我们确定了卵巢癌和宫颈癌标本中OVA 66和VEGF的表达水平之间的显着正相关性，并发现OVA 66与晚期卵巢cancer.Interpretation显著相关：我们确定了OVA 66在调节自分泌VEGF-VEGFR 2前馈信号循环，促进肿瘤进展和血管生成的新功能。(c)2019由Elsevier B. V.出版
Background: Activation of autocrine VEGF-VEGFR2 signalling in tumour cells activates cell proliferation, survival, and angiogenesis, all of which are crucial for tumour progression. Ovarian cancer-associated antigen 66 (OVA66) is now known to be overexpressed in multiple tumours and plays a role in tumour development, but the underlying mechanisms has not been fully investigated.Methods: We employed ovarian and cervical cancer cells and mouse models to detect the role of OVA66 in angiogenesis, growth, and metastasis of cancer cells. Immunofluorescence and western blot were used to determine the function of OVA66 in regulating autocrine VEGF-VEGFR2 signalling. Immunohistochemistry and bioinformatics analysis were used to detect the correlation of OVA66 and VEGF expression.Findings: OVA66 overexpression in the cancer cell lines promoted VEGF secretion, tumour growth and angiogenesis in vitro and in vivo. Conversely, shRNA-mediated OVA66 knockdown had the opposite effects. Mechanistically, OVA66 overexpression was found to boost an autocrine VEGF-VEGFR2 positive-feedback signalling loop in the tumour cells, leading to amplified effect of VEGF on tumour angiogenesis and proliferation and increased migration in vitro and in vivo, respectively. Finally, we identified a significant positive correlation between the expression levels of OVA66 and VEGF in ovarian and cervical cancer specimens, and found that OVA66 was significantly associated with advanced ovarian cancer.Interpretation: We identify a novel function for OVA66 in regulating an autocrine VEGF-VEGFR2 feed-forward signalling loop that promotes tumour progression and angiogenesis. (c) 2019 Published by Elsevier B.V.