Targeting stroma and tumor,silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma

作     者：Tahereh Setayesh Ying Hu Farzam Vaziri Xin Chen Jinping Lai Dongguang Wei Yu-Jui Yvonne Wan 

作者机构：Department of Medical Pathology and Laboratory MedicineUniversity of CaliforniaDavisSacramentoCA 95817USA Cancer Biology Programthe University of Hawaii Cancer CenterHonoluluHI 96813USA Department of Pathology and Laboratory MedicineKaiser Permanente Sacramento Medical CenterSacramentoCA 95825USA 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2024年第14卷第1期

页      面：292-303页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：The authors thank the Genomics Shared Resource(GSR)core facility at the University of California Davis Health Dr.Clifford G Tepper Stephanie Liu Ryan Davis for helping in performing spatial RNA sequencing and William Amato for his assistance in the quantification of immunohistochemistry slides.This manuscript is supported by grants funded by the USA National Institutes of Health(NIH)T32 CA108459e15 R01CA222490 R50CA243787.BioRender was used to draw mice figures in schematic experimental design 

主　　题：Liver Hepatocellular carcinoma Carbohydrate-binding lectin Galectin 1 Extracellular matrix Translation Spatial transcriptomics Tumor-margin 

摘      要：This study examines inhibiting galectin 1(Gal1)as a treatment option for hepatocellular carcinoma(HCC).Gal1 has immunosuppressive and cancer-promoting *** data showed that Gal1 was highly expressed in human and mouse *** levels of Gal1 positively correlated with the stages of human HCC and negatively with *** roles of Gal1 in HCC were studied using overexpression(OE)or silencing using Igals1 siRNA delivered by *** to HCC initiation induced by RAS and AKT mutations,lgals1-OE and silencing had opposite impacts on tumor *** treatment effect of lgals1 siRNAwas further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9%or even 42%of the body *** spatial transcriptomic profiles of Gal1 silenced and OE HCC,inhibiting matrix formation and recognition of foreign antigen in CD45t cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 *** the tumors,silencing Gal1 inhibited translational initiation,elongation,and ***,Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor,and the anti-HCC effect of lgals1 siRNAwas ***,Gal1 silencing has a promising potential for HCC treatment.