Hu Yong, He Meng-Ying, Zhu Li-Fang, Yang Cong-Chong, Zhou Mei-Ling, Wang Qiong, Zhang Wei, Zheng Yang-Yu, Wang Dong-Miao, Xu Zeng-Qi, Wu Yu-Nong, Liu Lai-Kui
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China.
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Postal#210029 136# Hanzhong Road, Nanjing, Jiangsu, the People's Republic of China.
J Exp Clin Cancer Res. 2016 Jan 15;35:12. doi: 10.1186/s13046-015-0281-z.
Both tumor-associated macrophages (TAMs) and the epithelial to mesenchymal transition (EMT) of cancer cells play key roles in promoting tumor progression. However, whether TAMs could induce EMT in the progression of oral squamous cell carcinoma (OSCC) remains undefined.
Here we detected the expression of macrophages markers CD68 and CD163, epithelial marker E-cadherin and mesenchymal marker vimentin in 127 OSCC patients by using semi-quantitative immunohistochemistry. CD68 and CD163 expression was not confined to the infiltrating TAMs, but also detected in cancer cells. The high number of CD68-positive macrophages was correlated with poor overall survival. Meanwhile, the expression of CD163 both in macrophages and in cancer cells was associated with poor overall survival and had a significant prognostic impact in OSCC. Importantly, the expression of CD163 in cancer cells had a significant relationship with E-cadherin and vimentin. Furthermore, the incubation of TAMs conditioned medium resulted in a fibroblast-like appearance of cancer cells (HN4, HN6 and SCC9) together with the decreased/increased expression of E-cadherin/ vimentin, which were correlated with the enhanced ability of migration and invasion.
Our results indicate that TAMs could promote the EMT of cancer cells, thereby leading to the progression of oral cancer.
肿瘤相关巨噬细胞(TAMs)和癌细胞的上皮-间质转化(EMT)在促进肿瘤进展中均起关键作用。然而,TAMs是否能在口腔鳞状细胞癌(OSCC)进展中诱导EMT仍不明确。
在此,我们通过半定量免疫组织化学检测了127例OSCC患者中巨噬细胞标志物CD68和CD163、上皮标志物E-钙黏蛋白和间质标志物波形蛋白的表达。CD68和CD163的表达不仅局限于浸润的TAMs,在癌细胞中也可检测到。CD68阳性巨噬细胞数量多与总体生存率低相关。同时,巨噬细胞和癌细胞中CD163的表达均与总体生存率低相关,且对OSCC有显著的预后影响。重要的是,癌细胞中CD163的表达与E-钙黏蛋白和波形蛋白有显著关系。此外,TAMs条件培养基的孵育导致癌细胞(HN4、HN6和SCC9)呈现成纤维细胞样外观,同时E-钙黏蛋白/波形蛋白的表达降低/增加,这与迁移和侵袭能力增强相关。
我们的结果表明,TAMs可促进癌细胞的EMT,从而导致口腔癌进展。