The PrPC is expressed in many types of immune cells including monocytes and macrophages, however, its function in immune regulation remains to be elucidated. In the present study, we examined a role for PrPC in regulation of monocyte function. Specifically, the effect of a soluble form of PrPC was studied in human monocytes. A recombinant fusion protein of soluble human PrPC fused with the Fc portion of human IgG1 (designated as soluble PrPC-Fc) bound to the cell surface of monocytes, induced differentiation to macrophage-like cells, and enhanced adherence and phagocytic activity. In addition, soluble PrPC-Fc stimulated monocytes to produce pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Both ERK and NF-κB signaling pathways were activated in soluble PrPC-treated monocytes, and inhibitors of either pathway abrogated monocyte adherence and cytokine production. Taken together, we conclude that soluble PrPC-Fc enhanced adherence, phagocytosis, and cytokine production of monocytes via activation of the ERK and NF-κB signaling pathways.
G protein-coupled receptors (GPCRs) are among the most significant therapeutic targets and some of them promote the growth and metastasis of cancer. Here, we show that an increase in the levels of GPR171 is crucial for lung cancer tumor progression in vitro and in vivo. Immunostaining of clinical samples indicated that GPR171 was overexpressed in 46.8% of lung carcinoma tissues. Depletion of GPR171 with an anti-GPR171 antibody decreased proliferation of lung carcinoma cells and attenuated tumor progression in a mouse xenograft model. Knockdown of GPR171 also inhibited migration and invasion of the lung cancer cell lines. Notably, inhibition of GPR171 synergistically enhanced the tumoricidal activity of an epidermal growth factor receptor (EGFR) inhibitor in lung cancer cells. These results indicate that GPR171 blockade is a promising antineoplastic strategy and provide a preclinical rationale for combined inhibition of GPR171 and EGFR.
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