P4HA3 promotes colon cancer cell escape from macrophage phagocytosis by increasing phagocytosis immune checkpoint CD47 expression

Mol Cell Biochem. 2024 Feb 12. doi: 10.1007/s11010-024-04927-z. Online ahead of print.ABSTRACTCancer immunotherapies have greatly changed the prospects for the therapy of many malignancies, including colon cancer. Macrophages as the effectors of cancer immunotherapy provide considerable promise for cancer treatment. Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) plays a cancer-promoting role in a variety of cancers, including colon cancer. In the present work, we provided evidence for the first time that P4HA3 promoted colon cancer cell escape from macrophage phagocytosis, and preliminarily explored its possible molecular mechanism. Immunohistochemistry was used to detect the expression of P4HA3 in tissues. Bioinformatics methods were used to analyze the tumor public databases (including TCGA database and GEO database). Macrophage phagocytosis assay and flow cytometric analysis were used to detect the phagocytic capacity of macrophages. Western blot and qRT-PCR were used to detect the expression of related markers (such as P4HA3, CD47, CD24, IL-34, and M-CSF). First, we found that P4HA3 was significantly and highly expressed in both colon cancer tissues and cells, and that P4HA3 had a positive correlation with lymph node metastasis, Dukes stage and also strongly correlated with poorer survival. Subsequently, we found that P4HA3 was strongly associated with the macrophage infiltration level in colon cancer. Immediately we also found that decreasing P4HA3 expression promoted macr...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Source Type: research