Proteoglycans of the extracellular matrix of cartilage provide this tissue with the ability to withstand and dissipate repetitive loading forces by reversible deformation. The genesis of an appropriate matrix requires the coordination of a variety of complex intra- and extracellular synthetic processes. One approach to examine these processes has been to use model systems which mimic some aspects of the normal tissue. Thus, the use of chondrosarcoma model has provided much information regarding the complex post-translational modification of a core protein necessary for its conversion into a proteoglycan. Such a model has its limitations since it represents rodent cartilage and not human material. Thus, it is desirable t be able to extend the number of available models to include ones for human cartilages. One difficulty in achieving this with normal human cartilage li s in the difficulty in maintaining phenotypic stability because of both the limited life span of normal cells and the propensity of chondrocytes to dedifferentiate in culture. One method of circumventing this problem of limited life span is to start with a neoplastic cell type, a chondrosarcoma cell, which expresses some features of the chondrocyte phenotype. These tumors however, have proven difficult to propagate in tissue culture primarily due to contamination of the cells with normal fibroblasts coupled with the relatively slow growth rate of the tumor cells. Technical developments in culture methodology have provided a means of dealing with many of these difficulties. We have successfully applied alternating cultur of chondrosarcoma cells in agarose suspension followed by monolayer to obta n a few cell lines from human tumors. Preliminary results with a battery of monoclonal antibodies against epitopes in fetal or adult cartilage have indicated that the tumor cell lines synthesize proteoglycans which react wi h all, while clonal cell lines derived from the parent population make proteoglycans which react with only a limited number. suggests This that th population of proteoglycans in the parent tumor may arise in part as a consequence of a heterogeneous cell population containing cells and their progeny which synthesize different proteoglycans. The cell lines obtained from this project will be examined to determine if this possibility can be generalized to all chondrosarcomas. In addition, this study will provide a methodological and perhaps conceptual framework to explore the possibility that normal cartilage may be composed of a heterogeneous cell population which-contributes to the proteoglycan heterogeneity present in the tissue.
