Chondromodulin-I Suppresses Tumorigenesis Of Human Osteosarcoma Cells

Osteosarcoma is the most common type of bone cancer, and accounts for similar to 3% of cancers that occurring in children. Chondromodulin-I (ChM-I) is a 25 kDa glycoprotein that is expressed mainly in cartilage. ChM-I demonstrates anti-angiogenic activity and has been suggested to inhibit endothelial cells from invading cartilage, and then has been shown to be an inhibitor of tumorigenesis. However, it remains unclear if ChM-I has any direct anti-tumorigenesis role on osteosarcoma. Therefore, the present study aimed to identify whether ChM-I has any direct inhibit effect on human osteosarcoma cells. A bromodeoxyuridine incorporation assay was performed on the Saos-2 human osteosarcoma cell line treated with or without recombinant human ChM-I, to evaluate its impact on DNA synthesis. An adenovirus carrier for the expression of ChM-I was constructed and transfected into tumor cells in vitro to evaluate the effect of ChM-I on tumor cells. Additionally, ChM-I was knocked down by using small interfering RNA to downregulate the expression of ChM-I. Cell invasion, migration and cell-colony formation assays, and xenograft tumor experiments were performed to evaluate the effects of ChM-I on tumor cells in vitro and in vivo. The results demonstrated that ChM-I could suppress DNA synthesis of human osteosarcoma cells, and it also exerted an inhibitory effect on the proliferation and colony formation abilities of human osteosarcoma cells. In addition, ChM-I inhibited cell invasion and migration in vitro and suppressed osteosarcoma cell growth significantly in vivo. In conclusion, ChM-I directly suppressed the proliferation and growth of osteosarcoma cells in an anchorage-independent manner, and may therefore be a promising drug for the treatment of osteosarcoma.