Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea
In Vivo. 2022 Sep-Oct;36(5):2194-2204. doi: 10.21873/invivo.12945.
BACKGROUND/AIM: A disintegrin and metalloprotease (ADAM) 12 expression has been found up-regulated in various cancer types. The aim of the study was to evaluate whether ADAM12 affects oncogenic behavior of gastric cancer (GC) cells and investigate its prognostic value.
The effect of ADAM12 on tumor cell behavior was examined using the small interfering RNA and pcDNA6-myc vector in human GC cell lines. Expression of ADAM12 in GC tissues was confirmed by immunohistochemistry. Apoptosis and proliferation were determined by a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and immunohistochemical staining for Ki-67.
ADAM12 overexpression enhanced tumor cell migration and invasion in AGS and SNU638 cells. Down-regulation of caspase-3 and PARP activity due to ADAM12 overexpression enhanced tumor cell proliferation and inhibited apoptosis. The expression of Snail and Vimentin increased and that of E-cadherin decreased following ADAM12 overexpression. In contrast, ADAM12 knockdown reversed these effects. ADAM12 overexpression increased the phosphorylation of Akt and GSK-3β. The mean Ki-67 labeling index value of ADAM12-positive tumors was significantly higher compared to that of ADAM12-negative tumors. ADAM12 expression was associated with age, tumor size, cancer stage, depth of invasion, lymph node metastasis, and poor survival.
ADAM12 enhances tumor progression by increasing cell mobility, enhancing cell proliferation, and inhibiting apoptosis in GC cells. Also, ADAM12 is associated with adverse clinicopathological features and poor survival. It may be used as a molecular marker for the prediction of clinical outcomes of patients with GC.
背景/目的：在各种癌症类型中发现解整合素金属蛋白酶 12（ADAM12）表达上调。本研究旨在评估 ADAM12 是否影响胃癌（GC）细胞的致癌行为，并研究其预后价值。
使用小干扰 RNA 和 pcDNA6-myc 载体在人 GC 细胞系中检测 ADAM12 对肿瘤细胞行为的影响。通过免疫组织化学法确认 GC 组织中 ADAM12 的表达。通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法和 Ki-67 的免疫组织化学染色检测细胞凋亡和增殖。
ADAM12 过表达增强了 AGS 和 SNU638 细胞的肿瘤细胞迁移和侵袭。ADAM12 过表达导致 caspase-3 和 PARP 活性下调，从而增强肿瘤细胞增殖并抑制细胞凋亡。E-钙黏蛋白表达下调，Snail 和波形蛋白表达增加。相反，ADAM12 下调逆转了这些作用。ADAM12 过表达增加了 Akt 和 GSK-3β 的磷酸化。ADAM12 阳性肿瘤的平均 Ki-67 标记指数值明显高于 ADAM12 阴性肿瘤。ADAM12 表达与年龄、肿瘤大小、癌症分期、浸润深度、淋巴结转移和不良生存相关。
ADAM12 通过增加 GC 细胞的迁移能力、增强细胞增殖和抑制细胞凋亡，促进肿瘤进展。此外，ADAM12 与不良的临床病理特征和不良生存相关。它可能作为预测 GC 患者临床结局的分子标志物。
