{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSecreted Protein Acidic and Rich in Cysteine (SPARC) is a multifunctional matricellular glycoprotein that plays a pivotal role in organizing the extracellular matrix. It binds to collagens and regulates ECM assembly, procollagen processing, and collagen fibrillogenesis – functions that are essential for normal bone formation, dentin development, and tissue repair. In mineralized tissues, for example, its regulated expression in osteoblasts and odontoblasts ensures proper differentiation and matrix deposition, thereby maintaining tissue integrity and promoting wound repair."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the tumor microenvironment, SPARC exhibits a complex, context‐dependent influence on tumor progression and metastasis. In a wide range of cancers – including melanoma, non‐small cell lung cancer, gliomas, breast, ovarian, gastric, pancreatic, and bladder carcinomas – SPARC expression in either tumor cells or the surrounding stroma modulates key processes such as cell adhesion, migration, invasion, and survival. Mechanistically, SPARC can promote epithelial‐to‐mesenchymal transition (via upregulation of factors like SLUG), activate intracellular kinases such as FAK, ILK and AKT, and even alter vascular permeability through interactions with VCAM1 and p38 MAPK signaling. Moreover, changes in SPARC expression by epigenetic silencing or microRNA‐mediated regulation underscore its potential as a prognostic biomarker with either tumor‐suppressive or tumor‐promoting functions, depending on the cellular context."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer, SPARC is equally critical in maintaining normal tissue homeostasis and regulating non‐malignant pathological processes. By mediating cell–matrix interactions through binding to integrin and scavenger receptors, SPARC orchestrates wound repair, modulates adipose tissue fibrosis and the metabolic dysregulation associated with obesity and diabetes, and may even contribute to disorders of other tissues such as the cornea. 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