Differential expression of aggrecan mRNA isoforms by chondrosarcoma cells.

Background: Aggrecan, the large aggregating proteoglycan, is a major component of the cartilage extracellular matrix. The C-terminal globular domain (G3) of the aggrecan molecule exhibits a pattern of alternative splicing that involves three exons. Each corresponds to a subdomain, epidermal growth factor I (EGF1), EGF2, and a short complement repeat (SCR). Materials and Methods: In the present study, we compared aggrecan mRNA splicing variants in osteochondrogenic tumor cells and normal cartilage using RT-PCR. Results: Normal cartilage expressed two mRNA isoforms, both containing the SCR exon, but with or without the EGF1 exon. Benign cartilaginous tumors showed the same splicing pattern as normal cartilage. However, malignant chondrosarcomas expressed additional splicing isoforms, one of which lacked all three alternative exons and another with EGF2 and SCR exons. The human chondrosarcoma cell line (Ch-1 cells) expressed further isoforms, one containing either EGF1 or EGF2 exon only, and another with all the variant exons. Conclusion: These results imply that a change in the pattern of alternative aggrecan mRNA splicing is associated with malignant transformation of chondrocytes.