{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:17:22Z","timestamp":1792808242529,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Department of Veteran Affairs Office of Research and Development","award":["I01BX006247"],"award-info":[{"award-number":["I01BX006247"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Siglec-15 has emerged as a therapeutic target in cancer, yet the glycan determinants and protein scaffolds that mediate engagement between Siglec-15-expressing myeloid cells and tumor cells remain incompletely defined. Here, we investigated the molecular basis of Siglec-15 recognition of cancer cells and examined transcriptional as well as functional programs associated with Siglec-15 expression in tumor-associated myeloid populations. Using immunoprecipitation-mass spectrometry in the pancreatic cancer cell line AsPC-1, we identified multiple mucin-domain glycoproteins enriched in Siglec-15 pulldowns. Additionally, disruption of glycan structures demonstrated that both complex N-glycans and extended mucin-type O-glycans contribute to optimal Siglec-15 binding.<\/jats:p>\n                  <jats:p>To define the myeloid population associated with Siglec-15 in human tumors, we interrogated publicly available single-cell RNA sequencing datasets and found that SIGLEC15 expression is enriched within a subset of tumor-associated myeloid cells exhibiting transcriptional features linked to osteoclast differentiation and extracellular matrix remodeling. Finally, in a THP-1 coculture model, Siglec-15 was further associated with DAP12-dependent tumor-induced expression of the osteoclast markers ACP5 and MMP9, together with increased release of IL-1\u03b2 and IL-6. Collectively, these findings identify glycan and glycoprotein features that support Siglec-15 binding to malignant cells and associate SIGLEC15 expression with osteoclast-like and matrix remodeling myeloid programs in human cancers, providing a framework for mechanistic studies of this glyco-immune checkpoint.<\/jats:p>","DOI":"10.1093\/glycob\/cwag035","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T11:47:48Z","timestamp":1781178468000},"source":"Crossref","is-referenced-by-count":1,"title":["Siglec-15 binds mucin-domain glycoproteins with extended glycans and marks an osteoclast-like, matrix remodeling myeloid state in human tumors"],"prefix":"10.1093","volume":"36","author":[{"given":"Nohelly","family":"Derosiers","sequence":"first","affiliation":[{"name":"Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania , 3600 Civic Center Boulevard, 15th Floor, Philadelphia, PA 19104-6160 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania , 3600 Civic Center Boulevard, 15th Floor, Philadelphia, PA 19104-6160 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon-Gyu S","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania , 3600 Civic Center Boulevard, 15th Floor, Philadelphia, PA 19104-6160 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgann","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania , 3600 Civic Center Boulevard, 15th Floor, Philadelphia, PA 19104-6160 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8711-629X","authenticated-orcid":false,"suffix":"Jr","given":"Avery D","family":"Posey","sequence":"additional","affiliation":[{"name":"Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania , 3600 Civic Center Boulevard, 15th Floor, Philadelphia, PA 19104-6160 ,","place":["United States"]},{"name":"Corporal Michael J. Crescenz VA Medical Center , 3900 Woodland Ave, Philadelphia, PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"issue":"11","key":"2026061513315070600_ref1","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.1172\/JCI35711","article-title":"NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism","volume":"118","author":"Aliprantis","year":"2008","journal-title":"J Clin Invest"},{"issue":"3","key":"2026061513315070600_ref2","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.bbrc.2008.02.111","article-title":"Siglec-9 enhances IL-10 production in macrophages via tyrosine-based motifs","volume":"369","author":"Ando","year":"2008","journal-title":"Biochem Biophys Res 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