TGF-?1 is the factor secreted by proliferative chondrocytes to inhibit neo-angiogenesis

Abstract

Growth plate is an avascular tissue, which has been reported to be capable of retarding tumor spread. It is believed that angiogenic inhibitor(s) exist to inhibit the neo-vascularization of tumor, thus impeding the tumor growth. In this study, growth plate chondrocyte-derived TGFbeta1 was identified to be anti-angiogenic. It was found that growth plate chondrocytes (GPC) secreted TGFbeta1 mostly in latent form as demonstrated by gel filtration and immunoblotting. Enzyme-linked immunosorbent assay (ELISA) was followed to quantify TGFbeta1 in GPC conditioned medium (CM), in which 866 pg/ml of TGFbeta1 was found. Besides, the angiogenesis inhibitory effect of GPC CM was abolished by the addition of anti-TGFbeta1 antibody in the in vitro culture system and the in vivo chick chorioallantoic membrane (CAM) assay. This confirmed the anti-angiogenic properties of chondrocyte-derived TGFbeta1. TGFbeta1 was expressed predominantly in the proliferative zone of porcine growth plate. This explains the low incidence of tumor invasion across the entire growth plate. Also, this helps to explain the observation that tumor invasion across the physis increases with age as the proliferative zone gradually disappears. J. Cell. Biochem. Suppl. 36: 79-88, 2001.