2. Academic Validation
  3. The diverse functions of Siglec-15 in bone remodeling and antitumor responses

The diverse functions of Siglec-15 in bone remodeling and antitumor responses

  • Pharmacol Res. 2020 May:155:104728. doi: 10.1016/j.phrs.2020.104728.
Fu-Biao Kang 1,  Wei Chen 2,  Ling Wang 3,  Ying-Ze Zhang 4
Affiliations

Affiliations

  • 1 The Liver Disease Center of PLA, the 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, Hebei, PR China.
  • 2 Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China.
  • 3 Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China; Department of Orthopedic Oncology, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China. Electronic address: wangling2016uw@126.com.
  • 4 Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, PR China. Electronic address: dryzzhang@126.com.
PMID: 32112821 DOI: 10.1016/j.phrs.2020.104728
Abstract

Siglec-15 is an immunoreceptor that binds to its ligand to exert diverse functions in osteoclast development, bone resorption, and even tumor-associated macrophage-mediated T cell immunity. Siglec-15 is a highly conserved member of the Siglec family and is constitutively expressed in osteoclasts, macrophages and dendritic cells. The activation domain in Siglec-15 can transmit a positive signal to regulate osteoclastogenesis via the formation of a complex with DAP12. In tumors, Siglec-15 is negatively regulated by IFN-γ, thus influencing effector T cell-mediated antitumor immunity. Importantly, this tumor-associated function of Siglec-15 is similar to that identified for PD-L1/PD-1 in normalization Cancer Immunotherapy. Cell-directed therapies are increasingly urgent and of clinical interest for their potential for reduced side effects and increased safety. Therefore, targeting Siglec‑15 might lead to novel discoveries for the clinical treatment of bone and tumor diseases or related diseases.

Keywords

Antitumor immunology; Bone remodeling; Siglec-15.

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