Department of Gastric Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
Department of Anatomy, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
Sci Rep. 2019 Mar 4;9(1):3414. doi: 10.1038/s41598-019-40265-7.
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.
基因失调的肿瘤细胞通过血管生成拟态（VM）生成血管通道，而这种血管生成与内皮血管无关。在 144 例胃腺癌临床样本和 AGS 胃癌细胞系中，评估了 VM 的形态特征和 EphA2 在 VM 形成中的作用。长期以来，人们一直认为 VM 由 PAS 阳性基底膜和 CD31/CD34 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管腔表面呈 PAS 阳性反应，并且 CD31/CD34 阳性肿瘤细胞参与了 VM 通道的形成。高度侵袭性的肿瘤细胞形成 VM 时被发现表达 CD31 或 CD34，这暗示了基因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 EphA2 的高表达呈正相关，通过 AGS 细胞中的基因沉默确定了 EphA2 在 VM 形成中的不可或缺作用。我们还报告了 EBV 阳性肿瘤细胞参与了 EBV 相关胃癌样本中 VM 通道的形成。总的来说，我们的结果表明 EphA2 信号通过在胃肿瘤发生过程中诱导 VM 形成来促进肿瘤转移。
