{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:45:45Z","timestamp":1765547145582,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["CA55819","CA200068"],"award-info":[{"award-number":["CA55819","CA200068"]}]},{"name":"US Department of Defense","award":["CA55819","CA200068"],"award-info":[{"award-number":["CA55819","CA200068"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Multiple myeloma (MM) induces dysfunctional bone marrow (BM) mesenchymal cells and neoangiogenesis. Pericytes and smooth muscle cells (SMCs) could detach from vessels and become cancer-associated fibroblasts. We found that the pericyte and SMC marker endothelin receptor type A (EDNRA) is overexpressed in whole MM bone biopsies; we sought to characterize its expression. EDNRA expression gradually increased with disease progression. High-risk MM patients had higher EDNRA expression than low-risk MM patients and EDNRA expression was highest in focal lesions. High EDNRA expression was associated with high expression of pericyte markers (e.g., RGS5, POSTN, and CD146) and the angiogenic marker FLT1. A single-cell analysis of unexpanded BM mesenchymal cells detected EDNRA expression in a subset of cells that coexpressed mesenchymal cell markers and had higher expression of proliferation genes. Immunohistochemistry revealed that the number of EDNRA+ cells in the interstitial BM increased as MM progressed; EDNRA+ cells were prevalent in areas near the MM focal growth. EDNRA+ cells were detached from CD34+ angiogenic cells and coexpressed RGS5 and periostin. Therefore, they likely originated from pericytes or SMCs. These findings identify a novel microenvironmental biomarker in MM and suggest that the presence of detached EDNRA+ cells indicates disrupted vasculature and increased angiogenesis.<\/jats:p>","DOI":"10.3390\/cancers15184519","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T03:54:06Z","timestamp":1694490846000},"page":"4519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["EDNRA-Expressing Mesenchymal Cells Are Expanded in Myeloma Interstitial Bone Marrow and Associated with Disease Progression"],"prefix":"10.3390","volume":"15","author":[{"given":"Wen","family":"Ling","sequence":"first","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah K","family":"Johnson","sequence":"additional","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2388-0480","authenticated-orcid":false,"given":"Syed J","family":"Mehdi","sequence":"additional","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisy V","family":"Alapat","sequence":"additional","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2498-7295","authenticated-orcid":false,"given":"Michael","family":"Bauer","sequence":"additional","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Zangari","sequence":"additional","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2699-1741","authenticated-orcid":false,"given":"Carolina","family":"Schinke","sequence":"additional","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharmilan","family":"Thanendrarajan","sequence":"additional","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frits","family":"van Rhee","sequence":"additional","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shmuel","family":"Yaccoby","sequence":"additional","affiliation":[{"name":"Myeloma Center, Department of Internal Medicine, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock 72205, AR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5418","DOI":"10.1182\/blood-2008-12-195008","article-title":"A monoclonal gammopathy precedes multiple myeloma in most patients","volume":"113","author":"Weiss","year":"2009","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1182\/blood-2016-09-692954","article-title":"MGUS to myeloma: A mysterious gammopathy of underexplored significance","volume":"128","author":"Dhodapkar","year":"2016","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e127807","DOI":"10.1172\/jci.insight.127807","article-title":"Early alterations in stem-like\/resident T cells, innate and myeloid cells in the bone marrow in preneoplastic gammopathy","volume":"5","author":"Bailur","year":"2019","journal-title":"JCI Insight"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s43018-020-0053-3","article-title":"Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma","volume":"1","author":"Zavidij","year":"2020","journal-title":"Nat. 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