Role of Putative Phosphorylation Sites on Tie2 Receptor in the Interaction between Tumor-Associated Macrophages and Human Endothelial Cells
2023
Mohseni, Zahra | Nasiri, Seyed Mehdi | Hoseini Pajooh, Khosro | Habibi-Kelishomi, Zahra | Goliaei, Bahram
BACKGROUND: Recently, a subpopulation of monocytes expressing Tie2 receptors has been identified, playing an important role in tumor angiogenesis. Selective depletion of Tie2-expressing monocytes in tumor-bearing mice can inhibit tumor angiogenesis. Some of these macrophages have been shown to be located near the tumor blood vessels, forming vessels in these areas paracrinely during the angiogenesis process.OBJECTIVES: This study aims to investigate the role of putative phosphorylation sites on Tie2 receptor in tumor- associated macrophages connected to human endothelial cells.METHODS: In this study, we used a series of Tie2 mutants. After transfection of tumor-associated macrophages with these mutants, they were evaluated for physical connection using the surface plasmon resonance technique and by non-contact co-culture of these macrophages with endothelial cells.RESULTS: Mutation in the tyrosine residues 1106 and 1111 had an inhibitory effect on macrophage binding to endothelial cells, resulting in deterioration of the angiogenic activity of these cells.CONCLUSIONS: Tie2 receptor and its downstream molecular pathways such as AKT/PI3 have a role in the interaction of tumor-associated macrophages with human endothelial cells, directly (via physical binding) and indirectly (through secretion of factors affecting angiogenesis). This emphasize the importance of the molecular mechanisms of Tie2 receptor activation in the interactions of endothelial cells with tumor-associated macrophages and as an anti-angiogenic therapy for cancer.
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