Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Korea.
Department of Pharmacology, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
J Oral Pathol Med. 2021 Sep;50(8):766-775. doi: 10.1111/jop.13176. Epub 2021 Mar 29.
Vasculogenic mimicry (VM) is the formation of an alternative circulatory system by aggressive tumor cells. The characteristics of VM and its underlying mechanism in oral squamous cell carcinoma (OSCC) remain unclear. This study aims to determine the relationship between VM in OSCC tissues and clinical outcomes and to investigate the biological role of SOX7 in VM in OSCC cells.
CD31/PAS staining was performed to evaluate VM in OSCC tissue. The relationships between VM and clinicopathological variables, and VM and SOX7 levels were analyzed. The correlation between SOX7 levels and cancer cohorts was investigated using in silico analysis. VM formation assay was performed to observe VM in vitro. To investigate the role of SOX7 in VM formation, SOX7 was transiently over-expressed in SCC-9 cells. VM-modulating genes were identified by Western blotting.
We found a positive correlation between VM and lymph node metastasis and patient survival in OSCC (p = 0.003). In silico analysis from The Cancer Genome Atlas and Gene Expression Omnibus database showed that down-regulation of SOX7 expression was significantly correlated with OSCC patients (p = 0.0187) and lymph node metastasis (p = 0.0017). We also found that the presence of VM in OSCC tissue was inversely associated with SOX7 expression (p = 0.020). We observed that overexpression of SOX7 impaired VM formation by reducing the expression of VE-cadherin, thereby inhibiting cell migration and invasion.
These results suggest that SOX7 plays an important role in the regulation of VM formation and may inhibit OSCC metastasis.
血管生成拟态（VM）是侵袭性肿瘤细胞形成替代循环系统的过程。口腔鳞状细胞癌（OSCC）中 VM 的特征及其潜在机制尚不清楚。本研究旨在确定 OSCC 组织中 VM 与临床结局的关系，并探讨 SOX7 在 OSCC 细胞中 VM 形成中的生物学作用。
采用 CD31/PAS 染色评估 OSCC 组织中的 VM。分析 VM 与临床病理变量之间的关系，以及 VM 与 SOX7 水平之间的关系。通过计算分析，研究 SOX7 水平与癌症队列之间的相关性。进行 VM 形成实验以观察体外 VM。为了研究 SOX7 在 VM 形成中的作用，我们在 SCC-9 细胞中转染瞬时过表达 SOX7。通过 Western blot 鉴定 VM 调节基因。
我们发现 VM 与 OSCC 中的淋巴结转移和患者生存呈正相关（p=0.003）。来自癌症基因组图谱和基因表达综合数据库的计算分析表明，SOX7 表达下调与 OSCC 患者（p=0.0187）和淋巴结转移（p=0.0017）显著相关。我们还发现 OSCC 组织中 VM 的存在与 SOX7 表达呈负相关（p=0.020）。我们观察到 SOX7 的过表达通过降低 VE-钙黏蛋白的表达来损害 VM 的形成，从而抑制细胞迁移和侵袭。
这些结果表明 SOX7 在调节 VM 形成中起重要作用，并可能抑制 OSCC 转移。
