Partial characterization of proteoglycans isolated from neoplastic and nonneoplastic human breast tissues

Abstract

The biochemical composition of proteoglycans was investigated in human breast tissues of different age either with invasive mammary carcinoma or with benign lesions of the breast. Proteoglycans were extracted from tissues under dissociative conditions (4 M guanidine-HCl), isolated by CsCl gradient ultracentrifugation, and purified by gel exclusion and ion exchange chromatography. Glycosaminoglycan side chain compositions of proteoglycans were evaluated by enzymatic analysis (chondroitinases ABC and AC) and nitrous acid degradation. Biochemical data indicated that proteoglycans of high density and molecular size were increased (per wet weight of tissue) in neoplastic compared to nonneoplastic tissues. Overall proteoglycan content was increased almost 2-fold in tumors. Furthermore, enzymatic data revealed a change in the proportions of glycosaminoglycan chains in neoplastic and nonneoplastic tissues. In particular, an increase in chondroitin sulfate (63% versus 35%, respectively) together with a decrease of dermatan sulfate (12% versus 45%, respectively) characterized tumors in comparison to mammary tissues with benign lesions, while the relative content of heparan sulfate side chains remained similar in both tissues. However, morphometric analyses revealed that heparan sulfate content per epithelial cell volume was in fact decreased in neoplastic tissue. These differences in proteoglycans indicate that there are significant changes in the extracellular matrix and surface properties of cells in breast cancer tissue.