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Hum Pathol. 2007 Jan;38(1):86-94. Epub 2006 Aug 1.

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

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Department of Pathology, Otto-von-Guericke-University, D-39120 Magdeburg, Germany.


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)-1beta and hypoxia on the regulation of ADAMTS1 and VEGF-A expression. ADAMTS1 was detected by reverse transcriptase-polymerase 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-1beta stimulation, not hypoxia, transcriptionally downregulated ADAMTS1 in chondrosarcoma cells, whereas VEGF-A expression was upregulated either by hypoxia or IL-1beta. We conclude that ADAMTS1 and VEGF-A in chondrosarcoma cells are regulated independently from each other. We believe that IL-1beta 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.

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