Akademik Veri Yönetim Sistemi
JOURNAL OF CELL COMMUNICATION AND SIGNALING, cilt.20, sa.2, 2026 (SCI-Expanded, Scopus)
Osteosarcoma (OS) is an aggressive bone malignancy characterized by genomic instability and extensive extracellular matrix (ECM) remodeling. Members of the ADAMTS family are matrix-associated proteases implicated in tumorigenesis; however, their roles in OS remain poorly defined. This study provides a comprehensive genomic, transcriptomic, and functional analysis of the ADAMTSs in OS, with particular focus on ADAMTS-3. Copy number alterations and mRNA expressions of ADAMTS genes were analyzed using the TCGA datasets. Gene set enrichment analysis and co-expression analyses identified biological processes associated with ADAMTS-3. Mechanistic studies investigated tumor necrosis factor-alpha (TNF-alpha) regulation of ADAMTS-3 in OS cells. Genomic profiling revealed frequent amplification and high mRNA expression of ADAMTS4, ADAMTS12, ADAMTS16, and ADAMTS17, indicating potential oncogenic activity. ADAMTS-3 was markedly overexpressed in OS tissues and cell lines, showing strong positive correlations with inflammatory (IL6, STAT3, NF-kappa B) and matrix-remodeling (MMP2, MMP9) genes. Functional enrichment indicated that ADAMTS-3 is associated with ECM organization, immune response regulation, and epithelial-mesenchymal transition. Mechanistically, TNF-alpha induced ADAMTS-3 transcription via activation of MEK, PI3K, JNK, and NF-kappa B pathways, with STAT3 and NF-kappa B by enhancing promoter activity. These findings identify ADAMTS-3 as an inflammation-responsive gene that links inflammatory signaling to ECM remodeling and tumor invasiveness in OS, representing a potential molecular bridge.