ADAMTS1 is regulated by interleukin-1 beta, not by hypoxia, in chondrosarcoma

Angiogenesis is characteristic of cartilage tumors, not of normal cartilage tissue. In addition to our previous report on differential expression of proangiogenic vascular endothelial growth factor A (VEGF-A) in cartilage tumors, we analyzed the expression of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), which has been identified as a potent inhibitor of VEGF-A. We further used a chondrosarcoma cell line to study the effect of interleukin (IL)-1 beta and hypoxia on the regulation of ADAMTS1 and VEGF-A expression. ADAMTS1 was detected by reverse transcriptasepolymerase chain reaction and immunohistochemistry in all analyzed samples from enchondromas, conventional chondrosacromas, and dedifferentiated chondrosarcomas without exception. In contrast to previous reports on other cancers, we did not detect a consistent decrease in ADAMTS1 expression in chondrosarcomas. Interleukin-1 beta stimulation, not hypoxia, transcriptionally downregulated ADAMTS1 in chondrosarcoma cells, whereas VEGF-A expression was upregulated either by hypoxia or IL-1 beta. We conclude that ADAMTS1 and VEGF-A in chondrosarcoma cells are regulated independently from each other. We believe that IL-1 beta has a stronger impact on vascularization in chondrosarcomas than hypoxia, as both factors, ADAMTS1 and VEGF-A, are regulated in a way that favors angiogenesis. (c) 2007 Elsevier Inc. All rights reserved.