Therapeutic modulation of APP-CD74 axis can activate phagocytosis of TAMs in GBM.

Autor: Ma C; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Chen J; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Ji J; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Zheng Y; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Liu Y; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Wang J; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Chen T; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Chen H; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Chen Z; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Zhou Q; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China., Hou C; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. Electronic address: dantengknight@hotmail.com., Ke Y; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. Electronic address: kyquan@smu.edu.cn.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Dec; Vol. 1870 (8), pp. 167449. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1016/j.bbadis.2024.167449
Abstrakt: Glioblastoma multiforme (GBM) remains the most lethal central nervous system cancer with poor survival and few targeted therapies. The GBM tumor microenvironment is complex and closely associated with outcomes. Here, we analyzed the cell-cell communication within the microenvironment and found the high level of cell communication between GBM tumor cells and tumor-associated macrophages (TAMs). We found that the amyloid protein precursor (APP)-CD74 axis displayed the highest levels of communication between GBM tumor cells and TAMs, and that APP and CD74 expression levels were significantly corelated with poorer patient outcomes. We showed that the expression of APP on the surface of GBM inhibited phagocytosis of TAMs through the binding of APP to the CD74/CXCR4 cell surface receptor complex. We further demonstrated that disrupting the APP-CD74 axis could upregulated the phagocytosis of TAMs in vitro and in vivo. Finally, we demonstrated that APP promotes the phosphorylation of SHP-1 by binding to CD74. Together, our findings revealed that the APP-CD74 axis was a highly expressed anti-phagocytic signaling pathway that may be a potential immunotherapeutic target for GBM.
Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be constructed as a potential conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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