COL10A1 beyond skeletal development: a hypertrophic chondrocyte-specific collagen emerging as a potential biomarker and tumor microenvironment regulator in solid cancers

Type X collagen (COL10A1) is an extracellular matrix protein primarily expressed by hypertrophic chondrocytes and is essential for endochondral ossification and skeletal mineralization. Although traditionally regarded as cartilage-specific, recent studies have reported its re-expression in a range of solid tumors. This shift in expression pattern suggests that COL10A1 may have functions beyond development, particularly within the tumor microenvironment (TME). Elevated COL10A1 levels have been reported in cancers such as breast, gastric, colorectal, and lung cancers, where both tissue expression and circulating levels are frequently associated with advanced disease stage and poor clinical outcomes. These observations support COL10A1 as a potential diagnostic and prognostic biomarker. Beyond its clinical associations, accumulating evidence indicates that COL10A1 actively contributes to tumor progression. It is involved in extracellular matrix remodeling, angiogenesis, epithelial-mesenchymal transition (EMT), and alterations in immune cell infiltration, and possibly immunotherapy response. In addition, its enrichment in specific subsets of cancer-associated fibroblasts (CAFs) highlights its essential role in tumor-stroma interactions. At the mechanistic level, COL10A1 has been linked to multiple oncogenic signaling pathways, including TGF-β1/SOX9, as well as downstream DDR2/FAK and ITGB1/PI3K/AKT pathways, which may collectively promote tumor invasion, metastasis, and therapy resistance. However, its biological functions are not yet fully defined, and tumor heterogeneity continues to complicate its clinical application. Further studies are needed to clarify how COL10A1-functions within the tumor microenvironment and to determine its clinical value as a biomarker and a potential therapeutic target in solid cancers.