Ye Hao, Li Xiang, Lin Jing, Yang Peng, Su Min
Institute of Clinical Pathology, Guangodng Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, No. 22 Xinling Road, Shantou, 515041, Guangdong, People's Republic of China.
The Judicial Critical Center, Shantou University Medical College, No. 22 Xinling Road, Shantou, 515041, Guangdong, People's Republic of China.
Cancer Cell Int. 2022 Feb 22;22(1):98. doi: 10.1186/s12935-021-02399-5.
The current study aims to find the linker between esophageal epithelial carcinogenesis and chronic inflammation and the origin of hyperproliferative cells in precancerous lesions of esophageal squamous cell carcinoma (ESCC).
Twenty one normal esophageal tissues from cadavers and 180 paired tissues from 60 surgical resected ESCC specimens were utilized for immunohistochemistry staining against CK14, CK6, CD98hc and Ki67. NE6 cell line was treated with HO to mimic chronic inflammation microenvironment and TPA for malignant orientated transformation. Cell proliferation and CD98hc mRNA were assessed by CCK8 assay and RT-qPCR.
CD98hc expression was correlated with chronic inflammation severity, precancerous lesion stage, and epithelial cell proliferative activity. CD98hc expression and proliferation rate of NE6 were up regulated by low dose HO treatment and long term TPA treatment. The proliferating cells in hyperplastic and dysplastic tissues could be divided into two patterns by the expression of CK14, CD98hc, CK6 and Ki67: CK14CD98hcCK6Ki67 in basal cells with CK14CD98hcCK6Ki67 in proliferating cells and CK14CD98hcCK6Ki67 in both basal cells and proliferating cells.
Our study revealed that CD98hc was a marker of cells originated from basal cell in esophagus, ectopic expression of CD98hc in hyperplastic/dysplastic cells by chronic inflammation stimulation crippled the linkage between basal cell and basement membrane, sabotaged the integrity of the barrier in between lamina propria and epithelium, subsequentially initiate carcinogenesis.
本研究旨在探寻食管上皮癌变与慢性炎症之间的联系以及食管鳞状细胞癌（ESCC）癌前病变中增殖细胞的起源。
使用来自尸体的21份正常食管组织以及60例手术切除的ESCC标本的180对配对组织进行针对细胞角蛋白14（CK14）、细胞角蛋白6（CK6）、CD98重链（CD98hc）和Ki67的免疫组织化学染色。用羟基脲（HO）处理NE6细胞系以模拟慢性炎症微环境，并用佛波酯（TPA）进行恶性定向转化。通过CCK8法和逆转录定量聚合酶链反应（RT-qPCR）评估细胞增殖和CD98hc信使核糖核酸（mRNA）。
CD98hc表达与慢性炎症严重程度、癌前病变阶段以及上皮细胞增殖活性相关。低剂量HO处理和长期TPA处理可上调NE6细胞的CD98hc表达和增殖率。增生和发育异常组织中的增殖细胞可根据CK14、CD98hc、CK6和Ki67的表达分为两种模式：基底细胞中CK14+CD98hc+CK6+Ki67+，增殖细胞中CK14+CD98hc+CK6+Ki67+，以及基底细胞和增殖细胞中CK14 - CD98hc - CK6 - Ki67 - 。
我们的研究表明，CD98hc是食管基底细胞来源细胞的标志物，慢性炎症刺激导致增生/发育异常细胞中CD98hc异位表达，破坏了基底细胞与基底膜之间的联系，损害了固有层和上皮之间屏障的完整性，继而引发癌变。
