{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSyndecan‑1 (SDC1) is a multifunctional transmembrane heparan sulfate proteoglycan that plays pivotal roles in maintaining cell–matrix adhesion, modulating growth factor signaling, and preserving endothelial integrity. Its extracellular domain not only binds numerous ligands, including growth factors such as hepatocyte growth factor and fibroblast growth factors, but also interacts with integrins and matrix‐modifying enzymes, thereby regulating cellular responses as diverse as viral attachment (e.g. during papillomavirus infection) and the preservation of the endothelial glycocalyx in trauma. In addition, SDC1 participates in the biogenesis of exosomes through its association with the syntenin‑ALIX machinery and is subject to regulation by proteolytic remodeling by matrix metalloproteinases and heparanase activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn hematological malignancies and plasma cell disorders, SDC1 is highly expressed and serves as a key marker for terminally differentiated B cells as well as malignant multiple myeloma cells. In these contexts the proteoglycan functions as a coreceptor that potentiates growth factor (notably HGF/Met) signaling and contributes to the regulation of tumor growth, dissemination, and angiogenesis. Moreover, its expression and shedding are integral to the formation of exosomes, thereby modulating the tumor microenvironment and influencing disease outcome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nProteolytic shedding of SDC1 is a highly regulated process that converts the membrane‐bound form into a soluble effector molecule. This shedding—mediated by enzymes such as MT1‑MMP, MT3‑MMP, ADAM family metalloproteinases, and MMP7—not only reduces cell–matrix adhesion at the cell surface but also promotes cell migration and invasion by releasing active SDC1 ectodomains. In addition, post‑transcriptional downregulation of SDC1 by oncomiRs (for example, miR‑10b) has been shown to enhance cell motility and invasiveness, marking a switch from a proliferative to a more invasive phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nActing as a key modulator of cell adhesion and intercellular communication, SDC1 directly couples with integrins (such as αvβ3 and αvβ5) to regulate cell spreading and inside‑out signaling. Its core protein provides a platform for the assembly of signaling complexes that control cytoskeletal organization and migration. Furthermore, SDC1 is involved in exosome formation and has diagnostic and prognostic implications in epithelial tumors—including ovarian and pancreatic cancers—where its altered expression reflects changes in the tumor stroma and aggressive disease behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSDC1 further contributes to tumor aggressiveness by modulating epithelial–mesenchymal transition (EMT), cancer stem cell properties, and resistance to therapy. Altered SDC1 expression and its shedding have been linked to the activation of signaling pathways including TGF‑β, IL‑6/STAT3, NFκB, and integrin‐mediated cascades. Moreover, heparanase‑induced reduction of nuclear SDC1 facilitates histone acetyltransferase activity and consequent changes in gene expression, while complex autocrine loops involving matrix metalloproteinases and cytokines (e.g. through the MMP‑7/Syndecan‑1/TGF‑β axis) promote EMT and chemoresistance. These multifaceted roles underscore SDC1’s central involvement in tumor progression and highlight its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "31", "end_ref": "46"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pär I Johansson, Jakob Stensballe, Lars S Rasmussen, et al. 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