The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages
| Autor: | Lei Liang, Qing-Qing Zhou, Xiang Luo, Hai-Biao Gong, Hiroshi Kurihara, Jiaxu Chen, Rong-Rong He, Yi-Fang Li, Tongzheng Liu, Hua-Ying Gao, Yan-Ping Wu |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
LRP1
RM1-950 Biology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Glucocorticoid receptor Phagocytosis SIRPα Signal-regulatory protein alpha medicine General Pharmacology Toxicology and Pharmaceutics Receptor Gene 030304 developmental biology 0303 health sciences Macrophages Psychological stress 030220 oncology & carcinogenesis Tumorigenesis Cancer research Therapeutics. Pharmacology Carcinogenesis Glucocorticoid Lipoprotein medicine.drug |
| Zdroj: | Acta Pharmaceutica Sinica B, Vol 12, Iss 1, Pp 197-209 (2022) |
| ISSN: | 2211-3835 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|