The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages.
10.1016/j.apsb.2021.06.002
- Author:
Yanping WU
1
;
Xiang LUO
1
;
Qingqing ZHOU
1
;
Haibiao GONG
1
;
Huaying GAO
1
;
Tongzheng LIU
2
;
Jiaxu CHEN
3
;
Lei LIANG
1
;
Hiroshi KURIHARA
1
;
Yi-Fang LI
1
;
Rong-Rong HE
1
Author Information
1. Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China.
2. Institute of Tumor Pharmacology, College of Pharmacy, Jinan University, Guangzhou 510632, China.
3. Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.
- Publication Type:Journal Article
- Keywords:
LRP1;
Macrophages;
Phagocytosis;
Psychological stress;
SIRPα;
Therapeutic target;
Tumorigenesis
- From:
Acta Pharmaceutica Sinica B
2022;12(1):197-209
- CountryChina
- Language:English
-
Abstract:
The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.
