Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki-shi, Nagasaki 852-8588, Japan.
Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki-shi, Nagasaki 852-8588, Japan.
Int J Oncol. 2018 Oct;53(4):1713-1720. doi: 10.3892/ijo.2018.4515. Epub 2018 Aug 6.
The cancer microenvironment (CME) promotes malignant progression of cancer cells by stimulating cell growth, migration and invasion. Cancer-associated fibroblasts (CAFs), prominent features of the CME, interact directly with cancer cells and facilitate epithelial-mesenchymal transition (EMT). The present study examined the spatial distribution of CAFs and EMT on cancer cells in patients with early-stage tongue squamous cell carcinoma (TSCC) and their association with local recurrence. The present study included 14 patients with early-stage TSCC who had undergone glossectomy between 2006 and 2015, of which 7 experienced local recurrence (LR group) and 7 did not (control group). Multiple immunofluorescent analysis (MIA) of PCNA, αSMA, vimentin, E-cadherin and cytokeratin 14 (CK14) was performed on slides obtained from surgical specimens to identify the expression of various cell-specific markers. The number of CAFs in the CME was significantly increased in the LR group (P=0.001). Furthermore, the neighbouring cancer cells were positive for vimentin expression, indicating EMT. However, the present study also identified concurrent expression of CK14 in all vimentin-positive cancer cells, whilst epithelial markers, including E-cadherin, were expressed in certain vimentin-positive cancer cells. Concurrent expression of CK14 and vimentin is not defined as EMT or partial EMT. Therefore, the present study proposed a novel mechanism of anaplastic transition (APT), in which epithelial cancer cells concurrently develop mesenchymal features, which is achieved by pathways other than EMT. APT is characterized such that epithelial cancer cells differentiate into more primitive states, which is different from EMT or partial EMT, and it may be associated with LR. The concept aids in improving knowledge regarding tumor recurrence in patients with early-stage TSCC.
肿瘤微环境（CME）通过刺激细胞生长、迁移和侵袭促进癌细胞的恶性进展。肿瘤相关成纤维细胞（CAF）是 CME 的主要特征之一，其与癌细胞直接相互作用，并促进上皮-间充质转化（EMT）。本研究检测了早期舌鳞状细胞癌（TSCC）患者肿瘤微环境中 CAF 和 EMT 在癌细胞上的空间分布及其与局部复发的关系。本研究纳入了 2006 年至 2015 年间接受舌部分切除术的 14 例早期 TSCC 患者，其中 7 例发生局部复发（LR 组），7 例未发生（对照组）。对手术标本切片进行多免疫荧光分析（MIA），检测 PCNA、αSMA、波形蛋白、E-钙黏蛋白和细胞角蛋白 14（CK14）的表达，以鉴定各种细胞特异性标志物的表达。LR 组 CME 中的 CAF 数量明显增加（P=0.001）。此外，邻近的癌细胞表达波形蛋白，表明发生 EMT。然而，本研究还发现，所有 vimentin 阳性癌细胞均同时表达 CK14，而上皮标志物 E-钙黏蛋白则在某些 vimentin 阳性癌细胞中表达。CK14 和波形蛋白的同时表达不能定义为 EMT 或部分 EMT。因此，本研究提出了一种新的间变转化（APT）机制，即在 EMT 以外的途径下，上皮性癌细胞同时获得间充质特征。APT 的特征是上皮性癌细胞分化为更原始的状态，与 EMT 或部分 EMT 不同，可能与 LR 相关。这一概念有助于提高对早期 TSCC 患者肿瘤复发的认识。
