Effect of Thiolated Glycosaminoglycans on the Behavior of Breast Cancer Cells: Toward the Development of in vitro Models of Cancer

Abstract

Purpose The influence of extracellular matrix components like glycosaminoglycans (GAG) or adhesive proteins on the migration of cancer cells and the progression of tumorigenesis remains a challenging task. Therefore, this study aims to give insight into the interaction of cancer cells exhibiting different metastatic potential (MDA-MB-231, MDA-MB-468) with surface immobilized GAG interacting with serum proteins like fibronectin. Methods Model substrata were covalently coated with different thiolated GAG (hyaluronan (HA), chondroitin sulfate (CS), heparin (Hep)) and investigated for the adsorption of fibronectin (FN) with surface plasmon resonance. Then, adhesion of breast cancer cells in the presence of and without serum proteins was studied. Further, the outgrow behavior of confluent cancer cells was examined with the help of cell migration chambers and single-cell migration with time-lapse microscopy. Results FN adsorption revealed that the Hep-coated surfaces were able to adsorb significantly more protein than CS and HA. Generally, initial adhesion of breast cancer cells on GAG-coated substrata was inhibited for HA- and CS-coated substrata in the presence of serum proteins for both cell lines in comparison to serum-free conditions. The cell size was also significantly decreased by the influence of serum proteins. The outgrow studies clearly confirmed the different migration speed of both cancer cells while single-cell migration was particularly enhanced on HA-coated surfaces. Conclusions The results reveal that adsorption of serum proteins (e.g. albumin) possess an inhibiting effect on the adhesion of breast cancer cells and that single-cell migration is enhanced for both breast cancer cell lines on HA.