Tanasubsinn Pattaramon, Aung Win Pa Pa, Pata Supansa, Laopajon Witida, Makeudom Anupong, Sastraruji Thanapat, Kasinrerk Watchara, Krisanaprakornkit Suttichai
Center of Excellence in Oral and Maxillofacial Biology, Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand.
Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Oncol Lett. 2018 Jan;15(1):495-502. doi: 10.3892/ol.2017.7284. Epub 2017 Oct 30.
Overexpression of a disintegrin and metalloproteinase 9 (ADAM9) has been shown in various types of cancer. Some studies have reported inconclusive findings regarding chromosomal aberrations in the -containing region and ADAM9 expression in oral cancer. Therefore, in this study, ADAM9 protein expression was determined and compared between oral squamous cell carcinoma (OSCC) and normal oral tissues, and between oral cancer cell lines and human oral keratinocytes (HOKs). In total, 34 OSCC and 10 healthy paraffin-embedded tissue sections were probed with an anti-ADAM9 antibody, and the immunohistochemical score was determined by multiplying the percentage of positively stained cells with the intensity score. Four different oral cancer and eight independent HOK cell lines were cultured, and the expression of membrane ADAM9 and active ADAM9 at 84 kDa in these cell lines was assayed by flow cytometry and western blot hybridization, respectively. The results showed that the median immunohistochemical score of ADAM9 expression in OSCC tissues was significantly greater than that in normal tissues (P<0.001). Furthermore, among OSCC cases, intense staining of ADAM9 expression was detected in well-differentiated and in moderately-differentiated OSCC; ADAM9 expression was also correlated with an increased degree of cell differentiation (=0.557; P=0.001). Expression of membrane ADAM9 was present in 3/4 cancer cell lines. Expression of active ADAM9 varied among all the tested cell lines, but significantly higher ADAM9 expression was present in certain cancer cell lines than those in HOKs (P<0.05). In summary, ADAM9 expression is enhanced in OSCC and oral cancer cell lines, suggesting its role in the pathogenesis of oral cancer. Similar to the overexpression of ADAM9 in well-differentiated prostate cancer, high degrees of ADAM9 expression have also been observed in well-differentiated OSCC.
去整合素金属蛋白酶9（ADAM9）在多种类型的癌症中均有过表达。一些研究报告了关于含该区域的染色体畸变与口腔癌中ADAM9表达的不确定结果。因此，在本研究中，测定并比较了口腔鳞状细胞癌（OSCC）与正常口腔组织之间，以及口腔癌细胞系与人口腔角质形成细胞（HOK）之间的ADAM9蛋白表达。总共用抗ADAM9抗体检测了34例OSCC和10例健康石蜡包埋组织切片，并通过将阳性染色细胞百分比与强度评分相乘来确定免疫组织化学评分。培养了4种不同的口腔癌细胞系和8种独立的HOK细胞系，分别通过流式细胞术和蛋白质印迹杂交检测这些细胞系中膜ADAM9和84 kDa活性ADAM9的表达。结果显示，OSCC组织中ADAM9表达的免疫组织化学评分中位数显著高于正常组织（P<0.001）。此外，在OSCC病例中，在高分化和中分化OSCC中检测到ADAM9表达的强染色；ADAM9表达也与细胞分化程度增加相关（=0.557；P=0.001）。3/4的癌细胞系中存在膜ADAM9表达。活性ADAM9的表达在所有测试细胞系中各不相同，但某些癌细胞系中的ADAM9表达明显高于HOK细胞系（P<0.05）。总之，ADAM9在OSCC和口腔癌细胞系中的表达增强，提示其在口腔癌发病机制中的作用。与ADAM9在高分化前列腺癌中的过表达类似，在高分化OSCC中也观察到了高度的ADAM9表达。
