Altered composition and increased endothelial cell proliferative activity of proteoglycans isolated from breast carcinoma.

Abstract

Proteoglycans of the extracellular matrix are vital to the growth and evolution of malignant neoplasms. The present study determined the composition of proteoglycans isolated from paired specimens of normal breast and adenocarcinoma of the breast harvested from each patient (n = 8). The proteoglycans were then tested for their ability to stimulate endothelial cell proliferation. Proteoglycans were isolated by extraction with 4 M guanidine hydrochloride and purified by CsCl density-gradient centrifugation. The proteoglycans were characterized and tested for their ability to simulate endothelial cell proliferation. In each case, the total proteoglycan content of the tumor was significantly greater than that of the corresponding normal tissue. The proteoglycans isolated from the carcinoma contained 32.2% (13.7/42.5) more chondroitin sulfate, 18.5% (5.6/30.2) less dermatan sulfate, and 29.6% (8.1/27.3) less heparan sulfate than did the proteoglycans of normal breast tissue. Proteoglycans from normal tissue did not stimulate endothelial cell proliferation, whereas those from malignant tissue stimulated proliferation by 1.3- to 1.5-fold. These results indicate that malignant breast tissue exhibits both qualitative and quantitative changes in proteoglycan composition, which, in turn, may stimulate endothelial cell proliferation.