ADAMTS1 is regulated by interleukin-1beta, 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)-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.
Kalinski
Thomas
T
Department of Pathology, Otto-von-Guericke-University, D-39120 Magdeburg, Germany. kalinski@medizin.uni-magdeburg.de
Krueger
Sabine
S
Sel
Saadettin
S
Werner
Kerstin
K
Röpke
Martin
M
Roessner
Albert
A
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D053583:Interleukin-1beta; D042461:Vascular Endothelial Growth Factor A; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human