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 osteoblastic reaction in the skeleton, a phenomenon which is followed by impairment of the mineralization process. We have proposed previously that soluble factors present in a medium conditioned by prostatic PC-3 cells (PC-3 CM) induce a rearrangement of bone extracellular matrix (ECM) which precedes the inhibition of mineralization. Interstitial collagen is the ECM component which is most affected by these prostatic factors. In this study, we evaluated the synthesis and molecular characteristics of proteoglycans (PG) derived from fetal rat osteoblasts cultured in the presence of PC-3 CM. These soluble factors induce a decrease (15-20%) in the production of PG. The in vitro produced PG display a decreased mean charge density and an increase in the hydrodynamic size of glycosaminoglycan (GAG) chains. No changes were observed in the size of the core protein or in the type of GAG chains of chondroitin sulfate. From these results, we suggest that fetal rat osteoblasts cultured in the presence of PC-3 CM synthesize PG which generate an ECM unable to support proper mineralization. We speculate that the modification of the ECM offers an advantage for tumor expansion.