Macrophage-derived cathepsin L promotes epithelial-mesenchymal transition and M2 polarization in gastric cancer  

作　　者：Lu-Xi Xiao Xun-Jun Li Hai-Yi Yu Ren-Jie Qiu Zhong-Ya Zhai Wen-Fu Ding Man-Sheng Zhu Wu Zhong Chuan-Fa Fang Jia Yang Tao Chen Jiang Yu 

机构地区：[1]Department of General Surgery,Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China [2]Department of Gastrointestinal and Hernia Surgery,Ganzhou Hospital-Nanfang Hospital,Ganzhou 341099,Jiangxi Province,China [3]Department of Gastrointestinal Surgery,Central Hospital of Wuhan,Wuhan 430014,Hubei Province,China [4]Department of General Surgery,Xiangyang Central Hospital,The Affiliated Hospital of Hubei University of Arts and Science,Xiangyang 441021,Hubei Province,China

出　　处：《World Journal of Gastroenterology》2024年第47期5032-5054,共23页世界胃肠病学杂志（英文）

基　　金：Supported by The National Natural Science Foundation of China,No.82272087 and No.82103150;The Guangdong Natural Science Foundation Outstanding Youth Project,China,No.2021B1515020055;The Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer,China,No.2020B121201004.

摘　　要：BACKGROUNDAdvanced gastric tumors are extremely prone to metastasize the in 20%–30% ofgastric cancer, and patients have a poor prognosis despite systemic chemotherapy.Peritoneal metastases from gastric cancer usually indicate the end stageof the disease without curative treatment.AIMTo peritoneal metastasis for facilitating clinical therapy are urgently needed.METHODSImmunohistochemical staining and immunofluorescence staining were used todemonstrate the high expression of cathepsin L (CTSL) in human gastric cancertissues and its localization in cells. Lentivirus transfection was used to construct stable cell lines. Transwell invasion assays, wound healing assays, and animal tests were used to determine therelationships between CTSL and epithelial-mesenchymal transition (EMT) and tumorigenic potential in vivo.RESULTSWe observed that macrophage-derived CTSL promoted gastric cancer cell migration and metastasis via the EMTpathway in vitro and in vivo, which involved macrophage polarization. Our findings suggest that macrophagesimprove extracellular matrix remodeling and hence facilitate tumor metastasis. Ablation of CTSL in macrophageswithin the tumor microenvironment may improve tumor therapy and the prognosis of patients with gastric cancerperitoneal metastasis.CONCLUSIONIn consideration of our findings, tumor-associated macrophage-derived CTSL is an important factor that promotesthe metastasis and invasion of gastric cancer cells, and the targeting of CTSL may potentially improve the prognosisof patients with gastric cancer with peritoneal metastasis.

关 键 词：Gastric cancer Invasion and metastasis Epithelial-mesenchymal transition Inflammation IMMUNOLOGY Tumorassociated macrophages Cancer prevention 

分 类 号：R735.2[医药卫生—肿瘤]