Li Xiuqing, Zhang Ji, Wu Youshan, Ma Chuntao, Wei Dongying, Pan Lijuan, Cai Liangliang
Department of Gastroenterology and Hepatology, Suzhou Xiangcheng People's Hospital, Suzhou, Jiangsu 215100, P.R. China.
Department of Gastroenterology and Hepatology, Yangzhou University Medical College, Yangzhou, Jiangsu 225001, P.R. China.
Oncol Lett. 2022 Jun 10;24(2):251. doi: 10.3892/ol.2022.13371. eCollection 2022 Aug.
Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer, and its development, growth, and invasiveness are regulated by the tumor microenvironment (TME). Insulin-like growth factor-binding protein-7 (IGFBP7), which is closely related to various tumors, transforming growth factor-β1 (TGFβ1), which is a key signal mediator in oncogenesis, α-smooth muscle actin (α-SMA), and collagen I are important components of the TME. IGFBP7 can upregulate the expression of TGFβ1 and activate the TGFβ1/SMAD signaling pathway, which leads to an increase in collagen I in hepatic stellate cells (HSCs). However, the contribution of IGFBP7 to TGFβ1 and the TME in the progression of ESCC remains unknown. In the present study, we investigated IGFBP7 expression and its effects on TGFβ1 and the TME in ESCC. A total of 45 patients were divided into three groups: early-tumor group (n=15), advanced-tumor group (n=15), and paracancer control group (n=15). The EC109 cell line was cultured and treated with AdIGFBP7 and LvshTGFβ1, and the expression levels of IGFBP7, TGFβ1, α-SMA, collagen I, and p-SMAD2/3 were determined by immunohistochemical staining and western blotting analysis. IGFBP7, TGFβ1, α-SMA, and collagen I were upregulated in the ESCC samples compared with the control samples (P<0.05), and the values peaked in the advanced-tumor group (P<0.05). Compared with the control group, the TGFβ1, α-SMA, p-SMAD2/3, and collagen I proteins were gradually increased from 24 to 72 h in the EC109 cells treated with AdIGFBP7 (P<0.05). Inhibition of TGFβ1 expression in the EC109 cells treated with AdIGFBP7 gradually reduced the expression of α-SMA, collagen I, and p-SMAD2/3 from 24 to 72 h (P<0.05). These findings suggest that increased IGFBP7 may accelerate the progression of ESCC by upregulating TGFβ1, α-SMA, and collagen I via activating the TGFβ1/SMAD signaling pathway, which could remodel the TME.
食管鳞状细胞癌（ESCC）是食管癌最常见的类型，其发生、发展和侵袭性受肿瘤微环境（TME）调控。胰岛素样生长因子结合蛋白7（IGFBP7）与多种肿瘤密切相关，转化生长因子-β1（TGFβ1）是肿瘤发生过程中的关键信号介质，α-平滑肌肌动蛋白（α-SMA）和I型胶原是TME的重要组成部分。IGFBP7可上调TGFβ1的表达并激活TGFβ1/SMAD信号通路，导致肝星状细胞（HSCs）中I型胶原增加。然而，IGFBP7在ESCC进展过程中对TGFβ1和TME的作用尚不清楚。在本研究中，我们调查了IGFBP7在ESCC中的表达及其对TGFβ1和TME的影响。共45例患者分为三组：早期肿瘤组（n = 15）、晚期肿瘤组（n = 15）和癌旁对照组（n = 15）。培养EC109细胞系并用AdIGFBP7和LvshTGFβ1处理，通过免疫组织化学染色和蛋白质印迹分析测定IGFBP7、TGFβ1、α-SMA、I型胶原和p-SMAD2/3的表达水平。与对照组相比，ESCC样本中IGFBP7、TGFβ1、α-SMA和I型胶原上调（P < 0.05），且在晚期肿瘤组中值达到峰值（P < 0.05）。与对照组相比，用AdIGFBP7处理的EC109细胞中TGFβ1、α-SMA、p-SMAD2/3和I型胶原蛋白在24至72小时逐渐增加（P < 0.05）。用AdIGFBP7处理的EC109细胞中TGFβ1表达的抑制在24至72小时逐渐降低α-SMA、I型胶原和p-SMAD2/3的表达（P < 0.05）。这些发现表明，IGFBP7增加可能通过激活TGFβ1/SMAD信号通路上调TGFβ1、α-SMA和I型胶原，从而加速ESCC进展，这可能重塑TME。
