title: Complex influence of dermatan sulphate on breast cancer cells.
abstract: Tumor transformation and progression both lead to extracellular matrix remodeling, which is also reflected in an alteration in the proportion of dermatan sulphate (DS) and chondroitin sulphate (CS) and an accumulation of the latter. In addition, a significant increase in the 6-O-sulphated disaccharide contribution to the structure of both glycosaminoglycans has been observed. It is commonly accepted that CS is more permissive for tumor growth than DS. However, the detailed role of DS in tumor progression is poorly known. We tested the effects of structurally different DSs on the behavior of cultured breast cancer cells. At a high dose (10 µg/mL), all of the DSs significantly reduced cancer cell growth, although some differences in the efficiency of action were apparent. In contrast, when used at a concentration of 1 µg/mL, the examined DSs evoked different responses ranging from the stimulation to the inhibition of cancer cell proliferation. The highest stimulatory activity was associated with fibrosis-affected fascia decorin DS, which is characterized by a particularly high content of 6-O-sulphated disaccharides. Further reduction in DS concentration to 0.5 µg/mL preserved majority of biological effects which were apparent at a dose of 1 µg/mL. The enzymatic fragmentation of the DSs, particularly by chondroitinase AC I, abolished the impact exerted by 1 µg/mL of the intact DS chains and sometimes resulted in the opposite effect. In contrast to DSs, highly sulphated C-6-S exhibited no effect on the cancer cells. Our data revealed the complexity of the effects of DSs on breast cancer cells, which include both co-receptor activity and the prevention of vascular endothelial growth factor action. In addition, the biological effect of DSs is strongly dependent not only on the glycosaminoglycan structure but also on its content in the cancer environment.
authors.affiliation: Department of Clinical Chemistry and Laboratory Diagnostics, Medical University of Silesia, Sosnowiec 41-200, ul. Jedności 8, Poland mkozma@sum.edu.pl.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Koźma
authors.affiliation: Department of Clinical Chemistry and Laboratory Diagnostics, Medical University of Silesia, Sosnowiec 41-200, ul. Jedności 8, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wisowski
authors.affiliation: Department of Cell Biology, Medical University of Silesia, Sosnowiec 41-200, ul. Jedności 8, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Latocha
authors.affiliation: Department of Orthopaedics and Traumatology, Medical University of Silesia, Katowice 40-635, ul. Ziołowa 45/47, Poland.
authors.forename: Damian
authors.initials: D
authors.lastname: Kusz
authors.affiliation: Department of Clinical Chemistry and Laboratory Diagnostics, Medical University of Silesia, Sosnowiec 41-200, ul. Jedności 8, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Olczyk
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003871:Dermatan Sulfate / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006133:Growth Substances / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006133:Growth Substances; D003871:Dermatan Sulfate
keywords: Dermatan sulphate; breast cancer; vascular endothelial growth factor