Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC.
Anticancer Res. 2010 Mar;30(3):727-36.
Once diagnosed, esophageal cancer has a very low overall 5-year survival rate. This study investigates the mechanisms behind the invasiveness and severity of esophageal squamous cell carcinoma (ESCC).
Transwell invasion chamber was used to subdivide one Taiwanese ESCC cell line, CE81T/VGH, into sublines (CE81T-0, CE81T-1, CE81T-2, CE81T-3, and CE81T-4) in four rounds of assays; the most invasive were identified, and various factors related to their invasiveness measured.
CE81T-1, CE81T-2, CE81T-3 and CE81T-4 sublines were significantly more invasive than the parental cells (CE81T/VGH) and CE81T-0 subline. CE81T-1 and CE81T-4, the sublines we chose to study further, had significantly greater colony-forming ability (3.5- to 2.7-fold) and wound migrating activity (1.95- to 2.6-fold) than the parental cells in vitro (p<0.01). They also displayed greater tumorigenesis in immunodeficient BALB/c Foxlnn mice than the parental cells. We found an inverse correlation between expression of tissue inhibitor of metalloproteinase-2 and invasive ability, and a significant positive correlation between expressions of matrix metalloproteinase-1, vimentin, and p-Src (pY416) in these cell lines and their invasiveness (all p<0.05).
The subline model may be used to study the molecular and genetic mechanisms underlying the invasion and metastasis of ESCC.
一旦被诊断出患有食管癌,其总体 5 年生存率非常低。本研究旨在探讨食管鳞状细胞癌(ESCC)侵袭性和严重性的机制。
采用 Transwell 侵袭小室将一个台湾 ESCC 细胞系 CE81T/VGH 分为四个亚系(CE81T-0、CE81T-1、CE81T-2、CE81T-3 和 CE81T-4);鉴定出最具侵袭性的细胞亚系,并测量与其侵袭性相关的各种因素。
CE81T-1、CE81T-2、CE81T-3 和 CE81T-4 亚系的侵袭性明显强于亲本细胞(CE81T/VGH)和 CE81T-0 亚系。CE81T-1 和 CE81T-4 亚系进一步研究发现,其体外集落形成能力(3.5-2.7 倍)和伤口迁移活性(1.95-2.6 倍)明显高于亲本细胞(p<0.01)。与亲本细胞相比,它们在免疫缺陷 BALB/c Foxlnn 小鼠中也显示出更强的致瘤性。我们发现这些细胞系中组织金属蛋白酶抑制剂-2 的表达与侵袭能力呈负相关,基质金属蛋白酶-1、波形蛋白和 p-Src(pY416)的表达与侵袭能力呈正相关(均 p<0.05)。
亚系模型可用于研究 ESCC 侵袭和转移的分子和遗传机制。