Zhao Xin, Liu Dongjuan, Wang Lili, Wu Ruiqing, Zeng Xin, Dan Hongxia, Ji Ning, Jiang Lu, Zhou Yu, Chen Qianming
State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.
J Oral Pathol Med. 2016 Apr;45(4):256-61. doi: 10.1111/jop.12371. Epub 2015 Oct 9.
Oral squamous cell carcinoma (OSCC) is one of the top ten tumors threatening human health. Oral cancer overexpressed 1 (ORAOV1) identified within chromosomal region 11q13, one of the most frequently amplified regions in OSCC, has been suggested as a novel candidate oncogene in OSCC, regulating cell cycle, apoptosis, and angiogenesis. In this study, we investigated the role of ORAOV1 in OSCC-induced angiogenesis in vitro.
EA.hy926 human endothelial cells were co-cultured with OSCC cells (HSC-3 and SCC-25) transfected with ORAOV1-specific shRNA to downregulate ORAOV1 expression, and analyzed for proliferation, migration, invasion, and tube formation by specific assays.
EA.hy926 endothelial cells co-cultured with ORAOV1-deficient OSCC cells exhibited significantly lower proliferation, migration, and invasion, as well as the activity in tube formation compared to that in the control cells.
Our results show, for the first time, that ORAOV1 expressed by OSCC cells promotes tube formation by endothelial cells, indicating its involvement in OSCC angiogenesis. Considering the importance of neovascularization in tumor development and metastasis, these findings suggest that targeting ORAOV1 may be a potential therapeutic strategy against OSCC.
口腔鳞状细胞癌（OSCC）是威胁人类健康的十大肿瘤之一。在11q13染色体区域发现的口腔癌过表达1（ORAOV1），该区域是OSCC中最常扩增的区域之一，已被认为是OSCC中的一种新型候选癌基因，可调节细胞周期、细胞凋亡和血管生成。在本研究中，我们在体外研究了ORAOV1在OSCC诱导的血管生成中的作用。
将EA.hy926人内皮细胞与转染了ORAOV1特异性shRNA以下调ORAOV1表达的OSCC细胞（HSC-3和SCC-25）共培养，并通过特定检测分析其增殖、迁移、侵袭和管腔形成情况。
与缺乏ORAOV1的OSCC细胞共培养的EA.hy926内皮细胞与对照细胞相比，其增殖、迁移和侵袭能力以及管腔形成活性均显著降低。
我们的结果首次表明，OSCC细胞表达的ORAOV1可促进内皮细胞的管腔形成，表明其参与了OSCC的血管生成。考虑到新生血管形成在肿瘤发展和转移中的重要性，这些发现表明靶向ORAOV1可能是一种针对OSCC的潜在治疗策略。
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