Targeting stroma and tumor, silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma.
10.1016/j.apsb.2023.10.010
- Author:
Tahereh SETAYESH
1
;
Ying HU
1
;
Farzam VAZIRI
1
;
Xin CHEN
2
;
Jinping LAI
3
;
Dongguang WEI
1
;
Yu-Jui YVONNE WAN
1
Author Information
1. Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA 95817, USA.
2. Cancer Biology Program, the University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
3. Department of Pathology and Laboratory Medicine, Kaiser Permanente Sacramento Medical Center, Sacramento, CA 95825, USA.
- Publication Type:Journal Article
- Keywords:
Carbohydrate-binding lectin;
Extracellular matrix;
Galectin 1;
Hepatocellular carcinoma;
Liver;
Spatial transcriptomics;
Translation;
Tumor-margin
- From:
Acta Pharmaceutica Sinica B
2024;14(1):292-303
- CountryChina
- Language:English
-
Abstract:
This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1-OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45+ cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment.
