Cancer-associated fibroblasts and epithelial-mesenchymal transition in metastatic oral tongue squamous cell carcinoma
Cancer-associated fibroblasts and epithelial-mesenchymal transition in metastatic oral tongue squamous cell carcinoma
复制标题
DOI：
10.1002/ijc.25358
复制
发表时间：
2010-09-15
影响因子：
6.4
通讯作者：
Salo, Tuula
中科院分区：
文献类型：
--
作者：
Vered, Marilena;Dayan, Dan;Salo, Tuula
我们检测了19对配对的口腔舌鳞状细胞癌（SCC）和区域淋巴结转移瘤（RLN）中的癌相关成纤维细胞（CAF）和一组上皮间质转化（EMT）的免疫组化标记物。研究α-平滑肌肌动蛋白（α-SMA）以鉴定CAF。用syndecan-1、Cadherin-11、成纤维细胞特异性蛋白（FSP）-1、富含半胱氨酸的酸性分泌蛋白（acidic and rich in cysteine，EMT）和Twist研究EMT。RLN中的三重免疫染色用于突出癌细胞（E-钙粘蛋白和Ki-67）及其与CAF（α-SMA）的关系。我们发现转移性RLN与配对的原发性肿瘤中的CAF相似。EMT标志物的表达在原发性和转移性肿瘤中是常见的。我们证明，转移性癌细胞（Ki-67阳性）下调E-cadherin表达的癌岛，在那里他们直接接触CAFs的周边。支持结缔组织微环境也通常表达多配体蛋白聚糖-1、钙粘蛋白-11、FSP-1和FSP-1。总之，CAF是常见的原发性和转移性SCC。我们假设CAFs不仅促进肿瘤的侵袭，而且还促进转移，无论是通过cometastasizing和/或被招募到淋巴结。EMT的证据在原发性肿瘤和转移性SCC中很常见，并且可能进一步受到CAF的调节。
We examined cancer-associated fibroblasts (CAFs) and a panel of immunohistochemical markers of epithelial-mesenchymal transition (EMT) in 19 pair matched oral tongue squamous cell carcinoma (SCC) and metastatic tumors to regional lymph nodes (RLNs). alpha-Smooth muscle actin (alpha-SMA) was studied to identify CAFs. EMT was studied with syndecan-1, Cadherin-11, fibroblast-specific protein (FSP)-1, secreted protein acidic and rich in cysteine (SPARC) and Twist. Triple immunostaining in RLNs was used to highlight the carcinoma cells (E-cadherin and Ki-67) and their relationship to the CAFs (alpha-SMA). We found that metastatic RLNs hosted CAFs similarly as in pair-matched primary tumors. Expression of EMT markers is common in both primary and metastatic tumors. We demonstrate that metastatic carcinoma cells (Ki-67 positive) downregulate E-cadherin expression at the periphery of cancer islands, where they are in direct contact with CAFs. The supporting connective tissue microenvironment also commonly expresses syndecan-1, Cadherin-11, FSP-1, and SPARC. In conclusion, CAFs are common to both primary and metastatic SCC. We hypothesize that CAFs not only promote tumor invasion but also facilitate metastases, either by cometastasizing and/or being recruited to lymph nodes. Evidence of EMT is common within primary tumors and metastatic SCC and may be further modulated by CAFs.