SOLUBLE FACTORS SECRETED BY PC-3 CELLS INDUCE STRUCTURAL-CHANGES IN PROTEOGLYCANS PRODUCED BY FETAL-RAT OSTEOBLASTS

Metastatic prostate cancer is unique in its ability to induce an osteo blastic reaction in the skeleton, a phenomenon which is followed by im pairment of the mineralization process. We have proposed previously th at soluble factors present in a medium conditioned by prostatic PC-3 c ells (PC-3 CM) induce a rearrangement of bone extracellular matrix (EC M) which precedes the inhibition of mineralization. Interstitial colla gen is the ECM component which is most affected by these prostatic fac tors. In this study, we evaluated the synthesis and molecular characte ristics of proteoglycans (PG) derived from fetal rat osteoblasts cultu red in the presence of PC-3 CM. These soluble factors induce a decreas e (15-20%) in the production of PG. The in vitro produced PG display a decreased mean charge density and an increase in the hydrodynamic siz e of glycosaminoglycan (GAG) chains. No changes were observed in the s ize of the core protein or in the type of GAG chains of chondroitin su lfate. From these results, we suggest that fetal rat osteoblasts cultu red in the presence of PC-3 CM synthesize PG which generate an ECM una ble to support proper mineralization. We speculate that the modificati on of the ECM offers an advantage for tumor expansion.