Chen Gang, Yan Ming, Li Rong Rong, Chen Wan Tao
Chin J Dent Res. 2018;21(1):31-40. doi: 10.3290/j.cjdr.a39916.
To investigate the Sonic Hedgehog (SHH) signalling molecules and activated leukocyte cell adhesion molecule (ALCAM) expression in the mechanisms regulating invasion and metastasis in oral squamous cell carcinoma (OSCC).
The expressions of SHH signalling molecules Gli family zinc finger 1/2 (Gli1/Gli2), as well as ALCAM expression, was analysed in 101 OSCC patients by immunohistochemistry. The potential relationship between Gli1/Gli2 and ALCAM in regard to invasion and metastasis were studied by western blot, invasion and wound-healing assays.
Gli1, Gli2 and ALCAM were expressed in 54.5%, 49.5% and 47.5% of the 101 OSCC specimens, respectively. High expression of ALCAM was associated with shorter survival in the patient population (P = 0.018), which was independent of other clinical parameters. Notably, when both ALCAM expression and positive nodal status were considered, an enhanced prediction of clinical outcomes was achieved (P = 0.001). In OSCC cell lines, down-regulation of ALCAM resulted in reduced cell invasion and metastasis. Importantly, SHH activation increased the half-life of ALCAM leading to ALCAM accumulation and increased cell invasion and migration.
ALCAM over-expression in OSCC is an independent prognostic factor for OSCC patients. Its over-expression may be the result of the activation of the SHH signalling pathway and contributes to OSCC progression.
研究音猬因子（SHH）信号分子及活化白细胞黏附分子（ALCAM）在口腔鳞状细胞癌（OSCC）侵袭和转移调控机制中的表达情况。
采用免疫组织化学法分析101例OSCC患者中SHH信号分子Gli家族锌指蛋白1/2（Gli1/Gli2）的表达以及ALCAM的表达情况。通过蛋白质免疫印迹法、侵袭实验和伤口愈合实验研究Gli1/Gli2与ALCAM在侵袭和转移方面的潜在关系。
在101例OSCC标本中，Gli1、Gli2和ALCAM的表达率分别为54.5%、49.5%和47.5%。ALCAM高表达与患者群体的生存期缩短相关（P = 0.018），且独立于其他临床参数。值得注意的是，当同时考虑ALCAM表达和阳性淋巴结状态时，对临床结局的预测能力增强（P = 0.001）。在OSCC细胞系中，ALCAM表达下调导致细胞侵袭和转移能力降低。重要的是，SHH激活增加了ALCAM的半衰期，导致ALCAM积累，并增加细胞侵袭和迁移能力。
OSCC中ALCAM过表达是OSCC患者的独立预后因素。其过表达可能是SHH信号通路激活的结果，并促进OSCC进展。
