EBV 通过增强干性和 EMT 促进休眠癌细胞的血管模拟。

EBV promotes vascular mimicry of dormant cancer cells by potentiating stemness and EMT.

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Xisi Road 20, Nantong, 226019, Jiangsu Province, China; Medical College of Nantong University, Nantong 226019, Jiangsu Province, China. Department of Pathology, Affiliated Hospital of Nantong University, Xisi Road 20, Nantong, 226019, Jiangsu Province, China; Department of Otorhinolaryngology Head and Neck Surgery, The First People's Hospital of Yancheng, Yancheng, Jiangsu Province, China.

Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Xisi Road 20, Nantong, 226019, Jiangsu Province, China; Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Xisi Road 20, Nantong, 226019, Jiangsu Province, China; Medical College of Nantong University, Nantong 226019, Jiangsu Province, China. Department of Pathology, Affiliated Hospital of Nantong University, Xisi Road 20, Nantong, 226019, Jiangsu Province, China.

出版信息

Exp Cell Res. 2022 Dec 15;421(2):113403. doi: 10.1016/j.yexcr.2022.113403. Epub 2022 Nov 4.

DOI:10.1016/j.yexcr.2022.113403

PMID:36336028

Abstract

Vascular mimicry (VM) is defined as a vascular channel-like structure composed of tumor cells that correlates with the growth of cancer cells by providing blood circulation. However, whether VM can be formed in dormant cancer cells remains unclear. Our previous research revealed that polyploid giant cancer cells (PGCCs) are specific dormant cells related to the poor prognosis of head and neck cancer. Here, we demonstrated that EBV could promote VM formation by PGCCs in vivo and in vitro. Furthermore, we revealed that the activation of the ERK pathway partly mediated by LMP2A is responsible for stemness, and the acquisition of the stemness phenotype is crucial to the malignant biological behavior of PGCCs. The epithelial-to-mesenchymal transition (EMT) process plays a considerable role in PGCCs, and EMT progression is vital for EBV-positive PGCCs to form VM. This is the first study to reveal that EBV creates plasticity in PGCC-VM and provide a new strategy for targeted anti-tumor therapy.

摘要

血管拟态（VM）被定义为由肿瘤细胞组成的类似于血管的通道结构，通过提供血液循环与癌细胞的生长相关。然而，休眠癌细胞是否能够形成 VM 尚不清楚。我们之前的研究表明，多倍体巨大癌细胞（PGCCs）是与头颈部癌症预后不良相关的特定休眠细胞。在这里，我们证明了 EBV 可以在体内和体外促进 PGCCs 形成 VM。此外，我们揭示了由 LMP2A 部分介导的 ERK 通路的激活负责干细胞特性，获得干细胞表型对于 PGCCs 的恶性生物学行为至关重要。上皮-间充质转化（EMT）过程在 PGCCs 中起着相当大的作用，EMT 进展对于 EBV 阳性 PGCCs 形成 VM 至关重要。这是第一项揭示 EBV 使 PGCC-VM 具有可塑性的研究，并为靶向抗肿瘤治疗提供了新策略。