Hagiwara Sumitaka, Murakumo Yoshiki, Sato Tomoko, Shigetomi Toshio, Mitsudo Kenji, Tohnai Iwai, Ueda Minoru, Takahashi Masahide
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Sci. 2008 Oct;99(10):1916-23. doi: 10.1111/j.1349-7006.2008.00949.x.
CD109 is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein whose expression is up-regulated in squamous cell carcinomas (SCCs) of the lung, esophagus, and uterus. The purpose of this study was to evaluate CD109 expression in oral tumors, including premalignant lesions, and to assess the clinical application of CD109 in oral cancer. CD109 expression in oral normal and tumor tissues from 124 patients was examined by immunohistochemical staining with anti-CD109 antibody, and significant relations between clinical features and CD109 expression were statistically assessed. We found that high levels of CD109 expression were frequently detected in SCCs and premalignant lesions of the oral cavity, but not in normal squamous epithelia. The CD109 expression level was higher in well-differentiated SCCs than in poorly differentiated SCCs. Furthermore, premalignant lesions highly expressing CD109 showed higher risk to progress to SCCs. Oral SCC cell lines overexpressing CD109 exhibited accelerated cell growth in vitro compared with control cell lines. In addition, overexpression of CD109 impaired the transforming growth factor (TGF)-beta1-mediated suppression of cell growth. These findings suggest that CD109 plays a role in the development of oral cancers, and is a useful prognostic marker to predict malignant transformation of premalignant lesions.
CD109是一种糖基磷脂酰肌醇(GPI)锚定糖蛋白,其在肺、食管和子宫的鳞状细胞癌(SCC)中表达上调。本研究的目的是评估CD109在包括癌前病变在内的口腔肿瘤中的表达,并评估CD109在口腔癌中的临床应用。用抗CD109抗体通过免疫组织化学染色检测了124例患者口腔正常组织和肿瘤组织中的CD109表达,并对临床特征与CD109表达之间的显著关系进行了统计学评估。我们发现,在口腔鳞状细胞癌和癌前病变中经常检测到高水平的CD109表达,但在正常鳞状上皮中未检测到。高分化鳞状细胞癌中的CD109表达水平高于低分化鳞状细胞癌。此外,高表达CD109的癌前病变进展为鳞状细胞癌的风险更高。与对照细胞系相比,过表达CD109的口腔鳞状细胞癌细胞系在体外表现出加速的细胞生长。此外,CD109的过表达削弱了转化生长因子(TGF)-β1介导的细胞生长抑制作用。这些发现表明,CD109在口腔癌的发生发展中起作用,并且是预测癌前病变恶性转化的有用预后标志物。