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Surprisingly, tumor cell proliferation was also reduced after endothelial deletion of CALCRL or Gs. We identified CCL2 as a critical angiocrine factor whose formation is inhibited by adrenomedullin. Furthermore, CCL2 inhibited adrenomedullin formation in tumor cells through its receptor CCR2. Consistently, loss of endothelial CCL2 or tumor cell CCR2 normalized the reduced tumor growth seen in mice lacking endothelial CALCRL or Gs. Our findings show tumor-promoting roles of adrenomedullin and identify CCL2 as an angiocrine factor controlling adrenomedullin formation by tumor cells.<\/jats:p>","DOI":"10.1084\/jem.20211628","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T14:52:17Z","timestamp":1668437537000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Suppression of CCL2 angiocrine function by adrenomedullin promotes tumor growth"],"prefix":"10.1084","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8030-9486","authenticated-orcid":true,"given":"Akiko","family":"Nakayama","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8659-3465","authenticated-orcid":true,"given":"Kenneth Anthony","family":"Roquid","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3087-4337","authenticated-orcid":true,"given":"Andr\u00e1s","family":"Iring","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3173-8094","authenticated-orcid":true,"given":"Boris","family":"Strilic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-4549","authenticated-orcid":true,"given":"Stefan","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Bioinformatics and Deep Sequencing Platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8267-8963","authenticated-orcid":true,"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Metabolic Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-5152","authenticated-orcid":true,"given":"Lee S.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8676-6805","authenticated-orcid":true,"given":"Stefan","family":"Offermanns","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany 1"},{"name":"Center for Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany 4"},{"name":"Cardiopulmonary Institute, Bad Nauheim, Germany 5"},{"name":"German Center for Cardiovascular Research, Bad Nauheim, Germany 6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2022,11,14]]},"reference":[{"key":"2022111414503272800_bib1","first-page":"36","article-title":"Image processing with ImageJ","volume":"11","author":"Abramoff","year":"2004","journal-title":"Biophot. 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