Epidermal growth factor-like domain 7 promotes cell invasion and angiogenesis in pancreatic carcinoma
Epidermal growth factor-like domain 7 promotes cell invasion and angiogenesis in pancreatic carcinoma
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表皮生长因子样结构域7促进胰腺癌细胞侵袭和血管生成
DOI：
10.1016/j.biopha.2015.12.009
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发表时间：
2016-02-01
影响因子：
7.5
通讯作者：
Zhi, Qiaoming
中科院分区：
文献类型：
--
作者：
Shen, Xiaochun;Han, Ye;Zhi, Qiaoming
表皮生长因子样结构域7（EGFL 7），又称血管内皮染色，是最早发现的平滑肌细胞迁移调节因子。尽管EGFL 7在胰腺癌发生过程中表达上调，但其在胰腺癌中的临床和生物学功能尚未完全阐明。在本研究中，我们发现PC组织中的血清EGFL 7水平显著高于正常人（p < 0.001），不可切除患者的血清EGFL 7水平也高于可切除患者（p = 0.013）。在这些可切除的PC患者中，当肿瘤被切除时，术后EGFL 7表达显著下调（p = 0.018）。免疫组化结果显示EGFL 7的阳性表达与TNM分期显著相关（p = 0.024），淋巴结转移（p = 0.003）和局部浸润经斯皮尔曼分析，EGFL 7表达与PC组织中微血管密度（MVD）密切相关（r = 0.941，p = 0.000）。在体外实验中，EGFL 7被siRNA沉默，下调EGFL 7的表达对PC细胞的周期进程、增殖、集落形成和凋亡无明显影响（p > 0.05），而抑制EGFL 7的表达可降低PaCa-2细胞的侵袭能力（p < 0.05）。更有趣的是，通过肾小管形成、鸡胚绒毛尿囊膜（CAM）和ELISA测定，我们的结果显示，沉默EGFL 7表达通过下调VEGF和Ang-2的蛋白水平对微血管的肾小管形成具有强烈的抑制作用（p < 0.05）。我们的研究结果提出了使用EGFL 7作为PC的潜在预后生物标志物和治疗靶点的可能性，并且下调EGFL 7可能被认为是PC患者的潜在重要分子治疗策略。(C)2015年Elsevier Masson SAS。All rights reserved.
Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, was firstly identified as a modulator of smooth muscle cell migration. Though the expression of EGFL7 was reported to be up-regulated during tumorigenesis, the clinical and biological functions of EGFL7 in pancreatic carcinoma (PC) were still not fully elucidated. In this study, we found that the serum EGFL7 level in PC tissues was statistically higher than that in normal subjects (p < 0.001), and its level in non-resectable patients was also higher than that in resectable ones (p = 0.013). Among these resectable PC patients, the postoperative EGFL7 expression was significantly down-regulated when tumors were resected (p = 0.018). Using the immunohistochemistry method, our results demonstrated that the positive expression of EGFL7 was significantly associated with the TNM stage (p = 0.024), lymph node metastasis (p = 0.003) and local invasion (p = 0.022), and the EGFL7 expression closely correlated to the micro-vessel density (MVD) in PC tissues by Spearman analysis (r = 0.941, p = 0.000). In vitro, EGFL7 was silenced by the small interference RNA in PC cells, and our data indicated that down-regulation of EGFL7 did not influence the cycle progression, proliferation, colony formation and apoptosis of PC cells (p > 0.05), whereas inhibition of EGFL7 expression could decrease PaCa-2 cell invasion (p < 0.05). More interestingly, by tubular formation, Chick embryo chorioallantoic membrane (CAM) and ELISA assays, our results revealed that silencing EGFL7 expression represented a strong inhibiting effect on tubular formation of micro-vessels through down-regulating the protein levels of VEGF and Ang-2 (p < 0.05). Our results raised the possibility of using EGFL7 as a potential prognostic biomarker and therapy target of PC, and down-regulation of EGFL7 might be considered to be a potentially important molecular treatment strategy for patients with PC. (C) 2015 Elsevier Masson SAS. All rights reserved.