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Siglec-15 recognition of extended mucin-type o-glycans and its association with an osteoclast-like myeloid state in cancer Nohelly Derosiers
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Derosiers, Nohelly, author.
- Language:
- English
- Subjects (All):
- Molecular biology.
- Immunology.
- Cellular biology.
- Pharmacology.
- Oncology.
- 0307.
- 0982.
- 0379.
- 0992.
- 0419.
- Local Subjects:
- Molecular biology.
- Immunology.
- Cellular biology.
- Pharmacology.
- Oncology.
- 0307.
- 0982.
- 0379.
- 0992.
- 0419.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (137 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Siglec-15 has garnered growing interest as a therapeutic target in cancer due to its ligand-mediated immunosuppressive effects. Yet, its role as a receptor on myeloid cells remains incompletely understood. This dissertation therefore aims to elucidate the receptor functions of this lectin by identifying glycan features and protein scaffolds that underlie Siglec-15 recognition of cancer cells, as well as examining transcriptional and functional programs associated with SIGLEC15 expression in tumor-associated myeloid populations. Immunoprecipitation-mass spectrometry in tumor cell lines combined with small molecule and enzymatic studies identified mucin-domain glycoproteins, complex N-glycans, and extended O-glycans as contributors to optimal Siglec-15 binding. Additionally, analysis of publicly available single-cell RNA-sequencing datasets revealed transcriptional programs associated with osteoclast differentiation and extracellular matrix remodeling in SIGLEC15-expressing myeloid cells. 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-1β and IL-6. Collectively, the findings in this work identify molecular determinants that support Siglec-15 binding to malignant cells and link SIGLEC15 expression with osteoclast-like, matrix-remodeling myeloid programs in human cancers, providing a framework for future mechanistic studies of this glyco-immune checkpoint
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Posey, Avery D., Jr.; Powell, Daniel J., Jr. Committee members: Fraietta, Joseph A.; Bellis, Susan
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247979708
- Access Restriction:
- Restricted for use by site license
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