Chen Jung-Tsu, Chen Chein-Hung, Ku Ko-Li, Hsiao Michael, Chiang Chun-Pin, Hsu Tsui-Ling, Chen Min-Huey, Wong Chi-Huey
Ph.D. Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei 100, Taiwan; Genomic Research Center, Academia Sinica, Taipei 115, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei 100, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei 100, Taiwan;
Genomic Research Center, Academia Sinica, Taipei 115, Taiwan;
Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):13057-62. doi: 10.1073/pnas.1516991112. Epub 2015 Oct 5.
The incidence and mortality rate of oral cancer continue to rise, partly due to the lack of effective early diagnosis and increasing environmental exposure to cancer-causing agents. To identify new markers for oral cancer, we used a sialylation probe to investigate the glycoproteins differentially expressed on oral cancer cells. Of the glycoproteins identified, B7 Homolog 3 (B7-H3) was significantly overexpressed in oral squamous cell carcinoma (OSCC), and its overexpression correlated with larger tumor size, advanced clinical stage, and low survival rate in OSCC patients. In addition, knockdown of B7-H3 suppressed tumor cell proliferation, and restoration of B7-H3 expression enhanced tumor growth. It was also found that the N-glycans of B7-H3 from Ca9-22 oral cancer cells contain the terminal α-galactose and are more diverse with higher fucosylation and better interaction with DC-SIGN [DC-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing nonintegrin] and Langerin on immune cells than that from normal cells, suggesting that the glycans on B7-H3 may also play an important role in the disease.
口腔癌的发病率和死亡率持续上升，部分原因是缺乏有效的早期诊断以及环境中致癌物质暴露的增加。为了鉴定口腔癌的新标志物，我们使用了一种唾液酸化探针来研究口腔癌细胞上差异表达的糖蛋白。在所鉴定的糖蛋白中，B7同源物3（B7-H3）在口腔鳞状细胞癌（OSCC）中显著过表达，其过表达与肿瘤体积较大、临床分期较晚以及OSCC患者的低生存率相关。此外，敲低B7-H3可抑制肿瘤细胞增殖，而恢复B7-H3表达则促进肿瘤生长。还发现，来自Ca9-22口腔癌细胞的B7-H3的N-聚糖含有末端α-半乳糖，并且比正常细胞的N-聚糖具有更多样化的岩藻糖基化以及与免疫细胞上的DC-SIGN [DC特异性细胞间粘附分子-3（ICAM-3）抓取非整合素]和朗格汉斯蛋白更好的相互作用，这表明B7-H3上的聚糖可能在该疾病中也起重要作用。
