2024年11月1日 · To explore causality, we analyze scRNAseq data of mouse LLC1 tumors treated with EP2 and EP4 antagonists and discover that inhibition of PGE 2-EP2/EP4 reverses the downregulation of...

Anti-inflammatory, anti-thrombotic and vasoprotective effects have been proposed for the EP4 receptor, along with its recently described unfavorable tumor-promoting and pro-angiogenic roles. A possible explanation for the diverse biological functions of EP4 might be the multiple signaling pathways switched on upon EP4 activation.

This review summarizes PGE 2 /EP4 signal inhibition in relation to the cancer-immunity cycle (C-IC), which describes fundamental tumor-immune interactions in cancer immunotherapy. PGE 2 is suggested to slow down C-IC by inhibiting natural killer cell functions, suppressing the supply of conventional dendritic cell precursors to the TME.

2020年5月29日 · In addition to tumor cell-autonomous roles of EP4, many EP4-positive host cells play a role in tumor behavior. Endothelial cell-EP4 supports tumor angiogenesis and lymphangiogenesis. Natural Killer (NK) cells are critical to the mechanism by which systemically administered EP4 antagonists inhibit metastasis.

2020年3月9日 · In animal studies, selective inhibition of the prostaglandin E receptor 4 (EP4), one of four PGE 2 receptors, suppresses tumor growth, restoring the tumor immune response toward an antitumorigenic condition.

In this study, using the immune checkpoint inhibitor-insensitive mouse cancer model and single-cell RNA sequencing, we show that PGE 2 -EP2/EP4 signaling simultaneously promotes active inflammation by inducing expression of the NF-κB genes in myeloid cells and elicits immunosuppression by driving the mregDC (mature DC enriched in immunoregulator...

2020年3月10日 · EP4 antagonist therapy is suggested to inhibit the immune-suppressive and tumorigenic roles of PGE 2 in tumors, and it may sensitize the therapeutic effects of ICIs in patients with non-inflamed and C-IC-deficient tumors. This review provides insight into the mechanism of action of EP4 antagonists in cancer immunotherapy and suggests a C-IC ...

EP4 overexpression has a number of potential effects that may enhance the development and spread of malignancy. PGE2 induces migration of tumor cells in vitro and endogenous EP4 signaling promotes metastasis in vivo. EP4 is highly expressed on human and mouse breast cancer cell lines.

Here we used the highly metastatic syngeneic murine C3L5 breast cancer model to test the role of EP4-expressing macrophages in vascular endothelial growth factor (VEGF)-C/D production, angiogenesis, and lymphangiogenesis in situ, the role of EP4 in stem-like cell (SLC) functions of tumor cells, and therapeutic effects of an EP4 antagonist RQ ...

2018年3月29日 · These cellular events are stimulated in COX-2 expressing breast tumors by activation of EP4 on tumor cells and tumor-associated host cells (immune cells, endothelial cells), so that EP4 presents as a therapeutic target to block multiple cellular events in tumor progression.