Differential expression of VEGF-A and angiopoietins in cartilage tumors and regulation by interleukin-1β

Abstract

BACKGROUND. Vascular endothelial growth factor (VEGF)-A and angiopoietin (Ang)-1 and Ang-2 are key factors in angiogenic signaling. In this study the expression of these factors was identified in cartilage tumors. As interleukin (IL)-1β has been found to be an indispensable factor in angiogenic signaling, we further analyzed the effect of IL-1β on the expression of VEGF-A, Ang-1, and Ang-2 using a previously established cell culture model. METHODS. Surgical specimens of enchondromas, conventional chondrosarcomas, and dedifferentiated chondrosarcomas were obtained from 72 patients. VEGF-A, Ang-1, and Ang-2 mRNA expression was detected by conventional and quantitative reverse transcription polymerase chain reaction (PCR). VEGF-A expression was also detected by immunohistochemistry or Western blot. RESULTS. Differential expression of VEGF-A, Ang-1, and Ang-2 was clearly demonstrated in cartilage tumors. VEGF-A expression was positively correlated with the tumor type. Higher VEGF-A expression levels were detected in conventional chondrosarcomas Grades II and III (using a 3-tier grading system) than in dedifferentiated chondrosarcomas (P < .05). A typical pattern of VEGF-A isoforms was identified, including VEGF121, VEGF145, VEGF 165, and VEGF189. Ang-1 presented as a low-level transcript with slightly elevated levels in chondrosarcomas (P < .05). Highly variable Ang-2 expression levels were detected in solitary cases of conventional chondrosarcomas. IL-1β regulated VEGF-A and Ang-1 expressions in a dose-dependent manner. Whereas low IL-1β concentrations increased VEGF-A and Ang-1 transcription, high IL-1β concentrations had the opposite effect. IL-1β did not activate Ang-2 expression. CONCLUSIONS. Angiogenic signaling in cartilage tumors is variable and at least partly regulable by IL-1β. The findings are of therapeutic relevance, either as a desired effect or a side effect in medical treatment. © 2006 American Cancer Society.