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 VEGF~121~, VEGF~145~, VEGF~165~, and VEGF~189~. 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. Cancer 2006. © 2006 American Cancer Society.