Morphological characteristics of vasculogenic mimicry and its correlation with EphA2 expression in gastric adenocarcinoma
Morphological characteristics of vasculogenic mimicry and its correlation with EphA2 expression in gastric adenocarcinoma
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DOI：
10.1038/s41598-019-40265-7
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发表时间：
2019-03-04
影响因子：
4.6
通讯作者：
Kim, Byung Sik
中科院分区：
文献类型：
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作者：
Kim, Hee Sung;Won, You Jin;Kim, Byung Sik
基因失调的肿瘤细胞通过不依赖于内皮血管的血管生成拟态（VM）产生血管通道。本研究对144例胃腺癌及AGS胃癌细胞系VM的形态学特征及EphA 2在VM形成中的作用进行了研究。VM由PAS阳性基底膜和CD 31/CD 34阴性细胞组成。有趣的是，我们发现形成VM通道的胃肿瘤细胞的腔表面显示PAS阳性反应，并且CD 31/CD 34阳性肿瘤细胞参与VM通道的形成。形成VM的高度侵袭性肿瘤细胞被发现表达CD 31或CD 34，暗示了遗传失调的肿瘤细胞的血管生成和血管生成潜力。在我们的患者队列中，VM的发生与EphA 2的高表达正相关，并且通过AGS细胞中的基因沉默来鉴定EphA 2在VM形成中不可或缺的作用。我们还报告了EB病毒（EBV）阳性肿瘤细胞参与了EBV相关胃癌样品中VM通道的形成。总的来说，我们的研究结果表明，EphA 2信号通过诱导胃肿瘤发生过程中VM的形成促进肿瘤转移。
Genetically deregulated tumor cells generate vascular channels by vasculogenic mimicry (VM) that is independent of endothelial blood vessels. The morphological characteristics of VM and the role of EphA2 in the formation of VM were evaluated in 144 clinical samples of gastric adenocarcinoma and AGS gastric cancer cell line. It has long been believed that VM consists of PAS-positive basement membrane and CD31/CD34-negative cells. Interestingly, we found that the luminal surface of gastric tumor cells that form VM channels showed PAS-positive reaction, and that the involvement of CD31/CD34-positive tumor cells in the formation of VM channels. Highly aggressive tumor cells that formed VM were found to express CD31 or CD34, implicating the angiogenic and vasculogenic potential of the genetically deregulated tumor cells. VM occurrence was positively correlated with high expression of EphA2 in our patient cohort, and the indispensable role of EphA2 in VM formation was identified by gene silencing in AGS cells. We also report that Epstein-Barr virus (EBV)-positive tumor cells were involved in the formation of VM channels in EBV-associated gastric cancer samples. Overall, our results suggest that EphA2 signaling promotes tumor metastasis by inducing VM formation during gastric tumorigenesis.