ALTERED COMPOSITION AND INCREASED ENDOTHELIAL-CELL PROLIFERATIVE ACTIVITY OF PROTEOGLYCANS ISOLATED FROM BREAST-CARCINOMA

Background and Objectives: Proteoglycans of the extracellular matrix a re vital to the growth and evolution of malignant neoplasms. The prese nt study determined the composition of proteoglycans isolated from pai red specimens of normal breast and adenocarcinoma of the breast harves ted from each patient (n = 8). The proteoglycans were then tested for their ability to stimulate endothelial cell proliferation. Methods: Pr oteoglycans were isolated by extraction with 4 M guanidine hydrochlori de and purified by CsCl density-gradient centrifugation. The proteogly cans were characterized and tested for their ability to simulate endot helial cell proliferation. Results: In each case, the total proteoglyc an content of the tumor was significantly greater than that of the cor responding normal tissue. The proteoglycans isolated from the carcinom a 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 th an did the proteoglycans of normal breast tissue. Proteoglycans from n ormal tissue did not stimulate endothelial cell proliferation, whereas those from malignant tissue stimulated proliferation by 1.3- to 1.5-f old. Conclusions: These results indicate that malignant breast tissue exhibits both qualitative and quantitative changes in proteoglycan com position, which, in turn, may stimulate endothelial cell proliferation . J. Surg. Oncol. 1998;68:250-254. (C) 1998 Wiley-Liss, Inc.