癌症研究
CD24型
流式细胞术
活力测定
化学
CD44细胞
生物
细胞
免疫学
生物化学
作者
Christian Söhngen,David J. Thomas,Margaretha A. Skowron,Felix Bremmer,Markus Eckstein,Anja Stefanski,Marc D. Drießen,Gamal Anton Wakileh,Kai Stühler,Peter Altevogt,Dan Theodorescu,Rüdiger Klapdor,Axel Schambach,Daniel Nettersheim
出处
期刊:FEBS Journal
[Wiley]
日期:2023-06-26
卷期号:290 (20): 4864-4876
被引量:3
摘要
Alternative therapeutic options targeting urologic malignancies, such as germ cell tumours, as well as urothelial, renal and prostate carcinomas, are still urgently needed. The membrane protein CD24 represents a promising immunotherapeutical approach. The present study aimed to decipher the molecular function of CD24 in vitro and evaluate the cytotoxic capacity of a third-generation natural killer (NK) cell chimeric antigen receptor (CAR) against CD24 in urologic tumour cell lines. Up to 20 urologic tumour cell lines and several non-malignant control cells were included. XTT viability assays and annexin V/propidium iodide flow cytometry analyses were performed to measure cell viability and apoptosis rates, respectively. Co-immunoprecipitation followed by mass spectrometry analyses identified direct interaction partners of CD24. Luciferase reporter assays were used to functionally validate transactivation of CD24 expression by SOX2. N- and O-glycosylation of CD24 were evaluated by enzymatic digestion and mass spectrometry. The study demonstrates that SOX2 transactivates CD24 expression in embryonal carcinoma cells. In cells of different urological origins, CD24 interacted with proteins involved in cell adhesion, ATP binding, phosphoprotein binding and post-translational modifications, such as histone acetylation and ubiquitination. Treatment of urological tumour cells with NK-CD24-CAR cells resulted in a decreased cell viability and apoptosis induction specifically in CD24+ tumour cells. Limitations of the study include the in vitro setting, which still has to be confirmed in vivo. In conclusion, we show that CD24 is a promising novel target for immune therapeutic approaches targeting urologic malignancies.
科研通智能强力驱动
Strongly Powered by AbleSci AI