EXPRESSION OF CARTILAGE EXTRACELLULAR-MATRIX AND POTENTIAL REGULATORYGENES IN A NEW HUMAN CHONDROSARCOMA CELL-LINE

A human chondrosarcoma cell line has been established from an aggressi ve chondrosarcoma. The cells grow in a monolayer culture (doubling tim e: 2 days) and form aggregates. The aggregates consist of a rim of cel ls surrounding a hollow core. The cell line exhibits a unique pattern of mRNA expression with several molecules characteristic of the chondr ocyte phenotype. Consistent with the chondrocyte phenotype, mRNAs enco ding types IX and XI collagens were present along with an abundant exp ression of mRNAs encoding the core protein of the cartilage proteoglyc ans biglycan and aggrecan. No expression of mRNAs encoding types I or II fibrillar collagens or the proteoglycan decorin was observed. Sodiu m dodecyl sulfate-polyacrylamide gel electrophoretic analysis of [S-35 ]sulfate-radiolabeled material confirmed the translation of proteoglyc ans containing glycosaminoglycan chains. The expression of molecules t hat contribute to cartilage development and tumorigenesis was examined . The cell line produces abundant mRNA that encodes transforming growt h factor-beta 1, a member of a family of cartilage and bone inductive proteins. The expression of mRNA encoding two proteins associated spec ifically with chondrogenesis was detected: Cart-1, a homeobox protein involved in cartilage differentiation, and CD-RAP, a secreted molecule restricted under normal conditions to differentiating chondrocytes an d cartilage. Overexpression of p53, a tumor-suppressor gene, was detec ted. DNA analysis revealed a loss of heterozygosity at the chromosomal locus encoding p53, with the deletion of one p53 allele and the mutat ion of the remaining allele in both the parent tumor and the cell line . The malignant chondrosarcoma phenotype may be related to the unique gene expression pattern that is characteristic in many ways of differe ntiating chondroblasts, as well as to the inactivation of the p53 func tion that could contribute to the proliferative capacity of the cell L ine. This cell line may serve as a biological model for further invest igation of the etiology of human chondrosarcomas and for the synthesis and regulation of cartilage-specific genes.