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Abstract Ovarian cancer (OC) remains a formidable challenge in oncology due to its high lethality. This poor prognosis is driven primarily by insidious peritoneal metastasis and the rapid development of resistance to conventional therapies. This comprehensive review delves into the transformative roles of extracellular matrix (ECM) polysaccharides and glycoproteins as dynamic architects of the tumor microenvironment (TME), reshaping our understanding of OC progression from a macromolecular lens. We elucidate how structural modifications—such as the enzymatic fragmentation of hyaluronan (HA) into pro-invasive low-molecular-weight forms, aberrant cross-linking of fibrous glycoproteins via lysyl oxidases, and dysregulated proteoglycans like biglycan (BGN) and versican—orchestrate a shift from physiological homeostasis to a stiffened, pro-malignant scaffold that fuels cell adhesion, invasion, and immune evasion. Central to this narrative is the emerging paradigm of tumor-derived exosomes as masterful conductors of ECM remodeling. These nanoscale vesicles ferry a potent cargo of proteases (e.g., matrix metalloproteinases, MMPs), microRNAs, and glycoprotein fragments, systematically priming distant pre-metastatic niches and amplifying systemic dissemination. By integrating biophysical insights, enzymatic mechanisms, and vesicular communication, we highlight novel interconnections that propel OC aggressiveness. Looking forward, we spotlight the translational promise of exosome-encapsulated macromolecular signatures—ranging from unique glycosignatures and BGN fragments to innovative diagnostic panels like the Ovarian Cancer Score (OCS)—as ultrasensitive liquid biopsy biomarkers. These advancements pave the way for early detection, precise prognostication, and tailored interventions, offering hope to combat this devastating disease. This review not only synthesizes cutting-edge evidence but also charts future directions for harnessing ECM-exosome dynamics in breakthrough therapies.
Qi et al. (Tue,) studied this question.