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Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.
Yang, Hua; Wang, Lianchun.
Afiliação
  • Yang H; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
  • Wang L; Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, United States; Bryd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, United States. Electronic address: lianchunw@usf.edu.
Adv Cancer Res ; 157: 251-291, 2023.
Article em En | MEDLINE | ID: mdl-36725112
The heparan sulfate proteoglycans (HSPGs) are glycoproteins that consist of a proteoglycan "core" protein and covalently attached heparan sulfate (HS) chain. HSPGs are ubiquitously expressed in mammalian cells on the cell surface and in the extracellular matrix (ECM) and secretory vesicles. Within HSPGs, the protein cores determine when and where HSPG expression takes place, and the HS chains mediate most of HSPG's biological roles through binding various protein ligands, including cytokines, chemokines, growth factors and receptors, morphogens, proteases, protease inhibitors, and ECM proteins. Through these interactions, HSPGs modulate cell proliferation, adhesion, migration, invasion, and angiogenesis to display essential functions in physiology and pathology. Under physiological conditions, the expression and localization of HSPGs are finely regulated to orchestrate their physiological functions, and this is disrupted in cancer. The HSPG dysregulation elicits multiple oncogenic signaling, including growth factor signaling, ECM and Integrin signaling, chemokine and immune signaling, cancer stem cell, cell differentiation, apoptosis, and senescence, to prompt cell transformation, proliferation, tumor invasion and metastasis, tumor angiogenesis and inflammation, and immunotolerance. These oncogenic roles make HSPGs an attractive pharmacological target for anti-cancer therapy. Several therapeutic strategies have been under development, including anti-HSPG antibodies, peptides and HS mimetics, synthetic xylosides, and heparinase inhibitors, and shown promising anti-cancer efficacy. Therefore, much progress has been made in this line of study. However, it needs to bear in mind that the roles of HSPGs in cancer can be either oncogenic or tumor-suppressive, depending on the HSPG and the cancer cell type with the underlying mechanisms that remain obscure. Further studies need to address these to fill the knowledge gap and rationalize more efficient therapeutic targeting.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoglicanas de Heparan Sulfato / Neoplasias Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: Adv Cancer Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoglicanas de Heparan Sulfato / Neoplasias Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: Adv Cancer Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos