Specific loss of chondromodulin-I gene expression in chondrosarcoma and the suppression of tumor angiogenesis and growth by its recombinant protein in vivo.

Chondromodulin-I (ChM-I) was previously identified as an angiogenesis inhibitor in cartilage. Here, we demonstrated that the level of ChM-I transcripts was substantially reduced to 100 or even less in the lower-grade chondrosarcomas, in articular cartilage or other benign cartilage tumors. We implanted human chondrosarcoma OUMS-27 cells into nude mice that reproducibly produced tumors with cartilaginous matrix. Tumor-induced angiogenesis was evident when the tumors were excised 30 days after implantation. However, the local administration of recombinant human ChM-I almost completely blocked vascular invasion and tumor growth in vivo. Moreover, ChM-I also inhibited the growth of HT-29 colon adenocarcinoma in vivo, implying its therapeutic potential for solid tumors.