Prgomet Zdenka, Andersson Tommy, Lindberg Pia
Oral Pathology, Faculty of Odontology, Malmö University, Malmö, Sweden.
Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
Eur J Oral Sci. 2017 Aug;125(4):237-246. doi: 10.1111/eos.12352. Epub 2017 Jun 12.
WNT5A is a secreted signaling protein that promotes migration and invasion of oral squamous cell carcinoma (OSCC) cells through activation of non-canonical WNT signaling. Here, we examined expression of WNT5A, β-catenin, and E-cadherin by immunohistochemistry in 21 human diagnostic incision biopsies that each had regions of oral mucosa with a normal appearance adjacent to the affected tissue, dysplasia, and OSCC. We also investigated the effect of recombinant WNT5A (rWNT5A) on expression of the cell-adhesion proteins E-cadherin and β-catenin by western blot analysis. No expression of WNT5A protein was present in oral mucosa with a normal appearance or in mild grade dysplasia. However, expression of WNT5A increased along with increasing grade of dysplasia, and the highest expression was detected in OSCCs. Expression of membranous β-catenin and of E-cadherin was lower, whereas expression of cytoplasmic β-catenin was higher, in OSCCs than in non-cancerous regions. However, there was no correlation between expression of WNT5A and expression of either β-catenin or E-cadherin. Furthermore, treatment of OSCC cells with rWNT5A had no effect on the expression of β-catenin or E-cadherin. Taken together with previous results, we conclude that WNT5A influences the progression of OSCC without affecting the canonical WNT/β-catenin pathway and without down-regulating E-cadherin. WNT5A may have potential as a biological marker for malignant transformation of dysplasia to OSCC.
WNT5A是一种分泌型信号蛋白，通过激活非经典WNT信号促进口腔鳞状细胞癌（OSCC）细胞的迁移和侵袭。在此，我们通过免疫组织化学检测了21例人类诊断性切口活检组织中WNT5A、β-连环蛋白和E-钙黏蛋白的表达，这些活检组织中每个都有外观正常的口腔黏膜区域，与受影响组织、发育异常和OSCC相邻。我们还通过蛋白质印迹分析研究了重组WNT5A（rWNT5A）对细胞黏附蛋白E-钙黏蛋白和β-连环蛋白表达的影响。外观正常的口腔黏膜或轻度发育异常中未检测到WNT5A蛋白表达。然而，WNT5A的表达随着发育异常等级的增加而增加，在OSCC中检测到最高表达。与非癌区域相比，OSCC中膜性β-连环蛋白和E-钙黏蛋白的表达较低，而细胞质β-连环蛋白的表达较高。然而，WNT5A的表达与β-连环蛋白或E-钙黏蛋白的表达之间没有相关性。此外，用rWNT5A处理OSCC细胞对β-连环蛋白或E-钙黏蛋白的表达没有影响。结合先前的结果，我们得出结论，WNT5A影响OSCC的进展，而不影响经典WNT/β-连环蛋白途径，也不下调E-钙黏蛋白。WNT5A可能有潜力作为发育异常向OSCC恶性转化的生物标志物。
