Troponin I is present in human cartilage and inhibits angiogenesis

Cartilage is an avascular and relatively tumor-resistant tissue. Work from a number of laboratories, including our own, has demonstrated that cartilag e is an enriched source of endogenous inhibitors of angiogenesis. In the co urse of a study designed to identify novel cartilage-derived inhibitors of neu capillary growth, we have purified an inhibitory protein that was ident ified by peptide microsequencing and protein database analysis as troponin I (TnI), TnI is a subunit of the troponin complex (troponin-C and troponin- T being the other two), which, along with tropomyosin, is responsible for t he calcium-dependent regulation of striated muscle contraction; independent ly, TnI is capable of inhibiting actomyosin ATPase, Because troponin has ne ver previously been reported to be present in cartilage, we have cloned and expressed the cDNA of human cartilage TnI, purified this protein to appare nt homogeneity, and demonstrated that it is a potent and specific inhibitor of angiogenesis in vivo and in vitro, as well as of tumor metastasis in vi vo.