Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan; Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan.
Biochem Biophys Res Commun. 2019 Jan 29;509(1):82-88. doi: 10.1016/j.bbrc.2018.12.066. Epub 2018 Dec 23.
We had previously reported that in addition to p53 inactivation, overexpression of the DNA sensor protein-absent in melanoma 2 (AIM2)-contributes to tumorigenesis of oral squamous cell carcinoma (OSCC). Given that AIM2 is highly expressed in the OSCC tumors from patients with metastasis, we investigated whether AIM2 expression contributes to the progression of OSCC metastasis. In in vitro assays using OSCC cell lines, the high migration and invasion capacity of OSCC cells were dependent on the increased expression of AIM2, resulting in enhanced epithelial-mesenchymal transition (EMT), with EMT-related gene expression. Moreover, the in vivo short-term metastasis assay using orthotopic implantation into immunodeficient mice demonstrated that OSCC cells with high levels of AIM2 expression exhibited enhanced tumor growth in the tongue, resulting in decreased survival of the mice. Further, the cells overexpressing AIM2 dominantly invaded into the tumor lymphatic vessels, unlike OSCC cells with low AIM2 expression. Thus, the high expression of AIM2 in OSCC enhances progression of tumor growth.
我们之前曾报道，除了 p53 失活外，DNA 传感器蛋白缺失黑色素瘤 2（AIM2）的过表达也有助于口腔鳞状细胞癌（OSCC）的发生。鉴于 AIM2 在有转移的 OSCC 肿瘤中高度表达，我们研究了 AIM2 表达是否有助于 OSCC 转移的进展。在使用 OSCC 细胞系的体外实验中，OSCC 细胞的高迁移和侵袭能力依赖于 AIM2 的表达增加，导致上皮-间充质转化（EMT）增强，具有 EMT 相关基因表达。此外，使用免疫缺陷小鼠原位植入的体内短期转移测定表明，表达高水平 AIM2 的 OSCC 细胞在舌部表现出增强的肿瘤生长，导致小鼠存活率降低。此外，与低 AIM2 表达的 OSCC 细胞不同，过表达 AIM2 的细胞主要侵犯肿瘤淋巴管。因此，AIM2 在 OSCC 中的高表达增强了肿瘤生长的进展。
