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TGF-beta1 is the factor secreted by proliferative chondrocytes to inhibit neo-angiogenesis
W H Cheung1, K M Lee, K P Fung
1Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Hong Kong, ROC.
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.
Insights
Growth plate chondrocytes secrete latent TGFbeta1, an anti-angiogenic factor that inhibits tumor growth. This explains why tumors rarely invade growth plates, especially in younger individuals.
Area of Science:
- Cell Biology
- Oncology
- Developmental Biology
Background:
- The growth plate, an avascular tissue, is known to impede tumor spread.
- Angiogenic inhibitors within the growth plate are hypothesized to prevent tumor neovascularization.
Purpose of the Study:
- To identify and characterize the anti-angiogenic properties of factors derived from growth plate chondrocytes.
- To investigate the role of TGFbeta1 in inhibiting tumor angiogenesis within the growth plate.
Main Methods:
- Gel filtration and immunoblotting to analyze TGFbeta1 secretion by growth plate chondrocytes (GPC).
- Enzyme-linked immunosorbent assay (ELISA) to quantify TGFbeta1 levels in GPC conditioned medium (CM).
- In vitro cell culture and in vivo chick chorioallantoic membrane (CAM) assays to assess the anti-angiogenic effects of GPC CM, with and without anti-TGFbeta1 antibody.
Main Results:
- Growth plate chondrocytes (GPC) were found to secrete TGFbeta1 predominantly in a latent form.
- Quantification revealed 866 pg/ml of TGFbeta1 in GPC conditioned medium (CM).
- The anti-angiogenic effect of GPC CM was neutralized by anti-TGFbeta1 antibody in both in vitro and in vivo models, confirming TGFbeta1's role.
Conclusions:
- TGFbeta1 secreted by growth plate chondrocytes possesses significant anti-angiogenic properties.
- TGFbeta1 expression is concentrated in the proliferative zone of the porcine growth plate, contributing to its resistance to tumor invasion.
- The age-related decrease in the proliferative zone may correlate with increased tumor invasion across the physis.