车站3
骨肉瘤
Jurkat细胞
癌症研究
细胞凋亡
STAT蛋白
受体
细胞培养
生物
医学
内科学
免疫学
T细胞
免疫系统
生物化学
遗传学
作者
Shiqin Zheng,Yuxi Wei,Yu Jiang,Yi Hao
出处
期刊:Tumori Journal
[SAGE]
日期:2020-10-14
卷期号:: 030089162095287-030089162095287
被引量:1
标识
DOI:10.1177/0300891620952872
摘要
Targeting programmed death-ligand 1 (PD-L1) may be an effective intervention for osteosarcoma and PD-L1 expression is controlled by diverse regulatory factors. Low-density lipoprotein receptor-related protein 8 (LRP8) regulates osteoblast differentiation and it is unclear whether and how LRP8 could contribute to osteosarcoma pathogenesis. In this study, we investigated the LRP8/signal transducer and activator of transcription 3 (STAT3)/PD-L1 network in osteosarcoma.The expression of LRP8, STAT3, and PD-L1 was measured in osteosarcoma tissues and paired normal tissues. The effects of LRP8 on STAT3 and PD-L1 expression were investigated in an osteosarcoma cell line. The effects on immunosuppression were investigated in an in vitro co-culture system with Jurkat cell line and osteosarcoma cell line. The effects of LRP8 were blocked by a LRP8 neutralizing antibody, dominant-negative STAT3, or STAT3 inhibitor.LRP8 was overexpressed in osteosarcoma compared to normal tissues and its level was correlated with phospho-STAT3 (p-STAT3) level in osteosarcoma tissues. In osteosarcoma cell lines, LRP8 increased p-STAT3 level and promoted nuclear translocation of STAT3. STAT3 activation also increased PD-L1 mRNA, protein, and promoter activity. In addition, LRP8 enhanced PD-L1 expression via STAT3. In a co-culture system, LRP8 overexpression in an osteosarcoma cell line impaired viability and interleukin-2 secretion of Jurkat cells and induced apoptosis of Jurkat cells. The effects of LRP8 could be blocked by neutralizing LRP8 antibody or STAT3 inhibitor. Blocking LRP8 inhibits proliferation and induces apoptosis of osteosarcoma cells.Our results provide evidence for a novel regulation network of LRP8/STAT3/PD-L1 in osteosarcoma and LRP8 may be a potential therapeutic target in osteosarcoma.
科研通智能强力驱动
Strongly Powered by AbleSci AI