Effect of FAP Expression Levels in Cancer-associated Fibroblasts on the Malignant Progression of Esophageal Squamous Cell Carcinoma
10.3870/j.issn.1672-0741.24.07.026
- VernacularTitle:肿瘤相关成纤维细胞中FAP的表达水平对食管鳞癌恶性进展的影响
- Author:
Jiayi LI
1
;
Li ZHANG
;
Shupei LIU
Author Information
1. 河南科技大学临床医学院,河南科技大学第一附属医院,河南省微生态与食管癌防治重点实验室,河南省肿瘤表观遗传重点实验室,洛阳 471003
- Publication Type:Journal Article
- Keywords:
esophageal squamous cell carcinoma;
fibroblast activation protein;
cancer-associated fibroblast
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(1):13-21
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression level of fibroblast activation protein(FAP)in esophageal squamous cell carcinoma(ESCC)and its prognostic implications,and to further explore the role of FAP expression in cancer-associated fibro-blasts(CAFs)in driving the malignant progression of ESCC.Methods The expression levels of FAP in tumor and adjacent tis-sues of 31 types of tumors were assessed by utilizing the TCGA database,followed by an analysis of its influence on the progno-sis of ESCC.Fresh tumor and normal tissue samples were acquired from ESCC patients in high-incidence regions for extracting and purifying primary CAFs and normal fibroblasts(NFs).Phenotypic identification and functional analyses were conducted via qRT-PCR,Western blot,and immunofluorescence.Supernatants from NFs,CAFs,and CAFs treated with the FAP inhibitor(FAPi)were collected to establish an in vitro co-culture model with KYSE150 cells.The impact of differential FAP expression levels on the malignant progression of KYSE150 cells,encompassing proliferation,invasion,and migration were assessed by u-sing EdU assay,CCK-8 assay,colony formation assay,Transwell assay,and scratch assay.The in vivo expression of FAP in CAFs was detected in a subcutaneous tumor model of esophageal cancer in mice to elucidate its role in the malignant progression of ESCC.Results In 10 types of malignant tumors,including ESCC,the expression of FAP was markedly elevated in tumor tissues compared to adjacent non-tumorous tissues.Moreover,elevated FAP expression in ESCC was associated with a poor prognosis and may serve as an independent prognostic risk factor for ESCC patients.Primary CAFs and NFs were effectively isolated from ESCC tumor and adjacent tissues,and their phenotypic characteristics were precisely characterized.The results of co-culture experiments indicated that,in comparison to NFs and untreated cells,CAFs with elevated FAP expression markedly enhanced the proliferation,invasion,and migration of KYSE150 cells.Conversely,FAPi treatment significantly suppressed these malignant behaviors.In vivo experiments had demonstra-ted that the deactivation treatment of FAPi and CAFs exerted a significant inhibitory effect on tumor growth in tumor-bearing mice.Conclusion In ESCC,the high expression of FAP is positively correlated with the activation of CAFs and the poor prognosis of patients,thereby promoting the malignant progression of the tumor.
