{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:49:43Z","timestamp":1782805783784,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,25]],"date-time":"2023-03-25T00:00:00Z","timestamp":1679702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Association for Cancer Research (AIRC)","award":["20441"],"award-info":[{"award-number":["20441"]}]},{"name":"Italian Association for Cancer Research (AIRC)","award":["22059"],"award-info":[{"award-number":["22059"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Growing evidence suggests a role for peroxisome proliferator-activated receptor \u03b2\/\u03b4 (PPAR \u03b2\/\u03b4) in the angiogenesis, growth, and metastasis of solid tumors, but little is known about its role in multiple myeloma (MM). Angiogenesis in the bone marrow (BM) is characteristic of disease transition from monoclonal gammopathy of undetermined significance (MGUS) to MM. We examined the expression and function of PPAR \u03b2\/\u03b4 in endothelial cells (EC) from the BM of MGUS (MGEC) and MM (MMEC) patients and showed that PPAR \u03b2\/\u03b4 was expressed at higher levels in MMEC than in MGEC and that the overexpression depended on myeloma plasma cells. The interaction between myeloma plasma cells and MMEC promoted the release of the PPAR \u03b2\/\u03b4 ligand prostaglandin I2 (PGI2) by MMEC, leading to the activation of PPAR \u03b2\/\u03b4. We also demonstrated that PPAR \u03b2\/\u03b4 was a strong stimulator of angiogenesis in vitro and that PPAR \u03b2\/\u03b4 inhibition by a specific antagonist greatly impaired the angiogenic functions of MMEC. These findings define PGI2-PPAR \u03b2\/\u03b4 signaling in EC as a potential target of anti-angiogenic therapy. They also sustain the use of PPAR \u03b2\/\u03b4 inhibitors in association with conventional drugs as a new therapeutic approach in MM.<\/jats:p>","DOI":"10.3390\/cells12071011","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T01:38:36Z","timestamp":1679881116000},"page":"1011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Unraveling the Role of Peroxisome Proliferator-Activated Receptor \u03b2\/\u0394 (PPAR \u03b2\/\u0394) in Angiogenesis Associated with Multiple Myeloma"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0904-1074","authenticated-orcid":false,"given":"Patrizia","family":"Leone","sequence":"first","affiliation":[{"name":"Department of Interdisciplinary Medicine, School of Medicine, \u2018Aldo Moro\u2019 University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2293-9698","authenticated-orcid":false,"given":"Antonio Giovanni","family":"Solimando","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine\u2014Ionian Pole, School of Medicine, \u2018Aldo Moro\u2019 University of Bari, 70124 Bari, Italy"},{"name":"IRCCS Istituto Tumori \u2018Giovanni Paolo II\u2019 of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Prete","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, School of Medicine, \u2018Aldo Moro\u2019 University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Malerba","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, School of Medicine, \u2018Aldo Moro\u2019 University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Susca","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, School of Medicine, \u2018Aldo Moro\u2019 University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Derakhshani","sequence":"additional","affiliation":[{"name":"McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ditonno","sequence":"additional","affiliation":[{"name":"Hematology Unit, IRCCS Istituto Tumori \u2018Giovanni Paolo II\u2019 of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Terragna","sequence":"additional","affiliation":[{"name":"Ser\u00e0gnoli\u2019 Institute of Hematology, Bologna University School of Medicine, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cavo","sequence":"additional","affiliation":[{"name":"Ser\u00e0gnoli\u2019 Institute of Hematology, Bologna University School of Medicine, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Silvestris","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Human Pathology \u201cG. Barresi\u201d, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8639-1940","authenticated-orcid":false,"given":"Vito","family":"Racanelli","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Medicine, School of Medicine, \u2018Aldo Moro\u2019 University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s13287-021-02283-z","article-title":"Any closer to successful therapy of multiple myeloma? CAR-T cell is a good reason for optimism","volume":"12","author":"Marofi","year":"2021","journal-title":"Stem Cell Res. 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