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Updated: Oct 26, 2025

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway
Meng-Ke Fan1, Guo-Chuan Zhang2, Wei Chen3
1Department of Orthopedic Research Center, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) promotes osteosarcoma (OS) progression by inhibiting dual-specificity phosphatase 1 (DUSP1) and activating the MAPK pathway. Targeting Siglec-15 may offer a new therapeutic strategy for OS treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Osteosarcoma (OS) is characterized by recurrence and metastasis, leading to poor prognosis.
- Aberrant Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) expression is implicated in various cancers, but its role in OS is unclear.
Purpose of the Study:
- To investigate the expression and function of Siglec-15 in osteosarcoma (OS).
- To elucidate the molecular mechanisms underlying Siglec-15's role in OS progression.
Main Methods:
- Cell culture (143B, MNNG/HOS), xenograft mouse models, RNA-sequencing (RNA-Seq), immunohistochemistry, Kaplan-Meier analysis.
- Investigated the effects of Siglec-15 knockdown and overexpression on OS cell proliferation, migration, and invasion.
- Analyzed the relationship between Siglec-15, dual-specificity phosphatase 1 (DUSP1), and MAPK signaling pathways.
Main Results:
- Downregulation of Siglec-15 inhibited OS cell proliferation, migration, and invasion by affecting epithelial-mesenchymal transition (EMT).
- Siglec-15 overexpression promoted OS cell growth, migration, and invasion.
- Siglec-15 silencing led to decreased DUSP1 expression; DUSP1 overexpression rescued the inhibitory effects of Siglec-15 knockdown.
- Siglec-15 promotes OS progression by suppressing DUSP1-mediated inhibition of MAPK pathways (p38/MAPK, JNK/MAPK).
- High Siglec-15 and DUSP1 expression correlated with poor prognosis, lung metastasis, and advanced Enneking stage in human OS tissues.
Conclusions:
- Siglec-15 promotes osteosarcoma development and progression.
- Siglec-15 activates DUSP1 and the MAPK pathway, contributing to OS malignancy.
- Siglec-15 represents a potential novel therapeutic target for osteosarcoma.
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