Suppression of CCL2 angiocrine function by adrenomedullin promotes tumor growth

• DOI: 10.1084/jem.20211628
• Publication Date: 2022-11-14T14:52:17Z
• Authors: Akiko Nakayama; Kenneth Anthony R...; András Iring; Boris Strilic; Stefan Günther; Min Chen; Lee S. Weinstein; Stefan Offermanns
• Keywords: Adrenomedullin

Within the tumor microenvironment, cells and endothelial regulate each other. While induce angiogenic responses in cells, release angiocrine factors, which act on other stromal cells. We report that cell–derived adrenomedullin has a pro-angiogenic as well direct tumor-promoting effect, endothelium-derived CC chemokine ligand 2 (CCL2) suppresses adrenomedullin-induced cell proliferation. Loss of receptor CALCRL or G-protein Gs reduced Surprisingly, proliferation was also after deletion Gs. identified CCL2 critical factor whose formation is inhibited by adrenomedullin. Furthermore, through its CCR2. Consistently, loss CCR2 normalized growth seen mice lacking Our findings show roles identify an controlling