title: Sulfated sugars in the extracellular matrix orchestrate ovarian cancer development: 'when sweet turns sour'.
abstract: Considering the high mortality of ovarian cancer, novel approaches for diagnostics and therapy are urgently needed. Cancer initiation, progression, and invasion occur in a complex and dynamic microenvironment which depends on the interplay between host cell responses and tumor activity. Chondroitin sulfate (CS), a special highly sulfated sugar, forms an important intermediate player in this respect. Depending on the (micro)structural diversity of chondroitin sulfate chains, various ligands interact with this special group of glycosaminoglycans, making it a key molecule for many physiological and pathological processes, including cancer development. This review focuses on the various functions of chondroitin sulfate in tumor growth, angiogenesis, dissemination and immunosilencing of ovarian cancer. We also shed light on possible future diagnostic and therapeutic modalities for ovarian cancer based on the large variety in chondroitin sulfate microstructure and function. It is concluded that the class of chondroitin sulfate represents an attractive target to interfere with the process of ovarian tumorigenesis.
authors.affiliation: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Myrtille.vallen@radboudumc.nl.
authors.forename: Myrtille J E
authors.initials: MJ
authors.lastname: Vallen
authors.affiliation: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Sophieke C H A
authors.initials: SC
authors.lastname: van der Steen
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Angela A G
authors.initials: AA
authors.lastname: van Tilborg
authors.affiliation: Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Leon F A G
authors.initials: LF
authors.lastname: Massuger
authors.affiliation: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
mesh_terms: D063646:Carcinogenesis / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D002809:Chondroitin Sulfates / Q000276:immunology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006025:Glycosaminoglycans / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019139:Tumor Escape / Q000276:immunology
chemical_list: D006025:Glycosaminoglycans; D002809:Chondroitin Sulfates
keywords: Biomarkers; Carcinogenesis; Chondroitin sulfate; Glycosaminoglycans; Therapeutic targeting