Song Xiaopeng, Han Ping, Liu Jingmei, Wang Yunwu, Li Dongxiao, He Jiayi, Gong Jin, Li Mengke, Tu Wei, Yan Wei, Liu Mei, Huang Huanjun, Tian Dean, Liao Jiazhi
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan, 430030, Hubei Province, China.
J Mol Histol. 2015 Oct;46(4-5):347-56. doi: 10.1007/s10735-015-9627-2. Epub 2015 Jun 16.
Invasion and metastasis are the major causes of death in patients with esophageal squamous cell carcinoma (ESCC). Recent studies have confirmed that SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) plays multiple roles in cancer progression. This study aims to explore the clinical characteristics of SPOCK1 in ESCC and its roles in the migration and invasion of ESCC cell lines. In this study, the up-regulation of SPOCK1 expression was frequently detected in primary ESCC tumor tissues compared with those in non-tumor tissues, which was significantly associated with tumor invasion (p = 0.004) and distant metastasis (p = 0.010). SPOCK1 was expressed at higher level in TE13 cells as compared to the low malignant Eca109 and TE1 cells. Overexpression of SPOCK1 in Eca109 cells decreased the expressions of epithelial marker E-cadherin and ZO-1, while increased mesenchymal marker Vimentin and N-cadherin levels. After ectopic expression of SPOCK1, Eca109 cells exhibited a morphological change from an epithelial cobblestone phenotype to an elongated fibroblastic phenotype, concomitant with cytoskeletal rearrangements and increased migration and invasion, suggesting that EMT occurs. While silencing SPOCK1 in TE13 cells had the opposite effects. These results suggest that up-regulation of SPOCK1 in ESCC induces EMT, thus promotes migration and invasion in ESCC cells.
侵袭和转移是食管鳞状细胞癌（ESCC）患者死亡的主要原因。最近的研究证实，富含半胱氨酸的酸性分泌蛋白/骨连接蛋白、cwcv和Kazal样结构域蛋白聚糖1（SPOCK1）在癌症进展中发挥多种作用。本研究旨在探讨SPOCK1在ESCC中的临床特征及其在ESCC细胞系迁移和侵袭中的作用。在本研究中，与非肿瘤组织相比，原发性ESCC肿瘤组织中经常检测到SPOCK1表达上调，这与肿瘤侵袭（p = 0.004）和远处转移（p = 0.010）显著相关。与低恶性的Eca109和TE1细胞相比，SPOCK1在TE13细胞中表达水平更高。Eca109细胞中SPOCK1的过表达降低了上皮标志物E-钙黏蛋白和ZO-1的表达，同时增加了间充质标志物波形蛋白和N-钙黏蛋白的水平。SPOCK1异位表达后，Eca109细胞表现出从上皮鹅卵石表型到细长纤维母细胞表型的形态变化，同时伴有细胞骨架重排以及迁移和侵袭增加，提示发生了上皮-间质转化（EMT）。而在TE13细胞中沉默SPOCK1则产生相反的效果。这些结果表明，ESCC中SPOCK1的上调诱导EMT，从而促进ESCC细胞的迁移和侵袭。
