title: ADAMTS1 is regulated by interleukin-1beta, not by hypoxia, in chondrosarcoma.
abstract: 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.
authors.affiliation: Department of Pathology, Otto-von-Guericke-University, D-39120 Magdeburg, Germany. kalinski@medizin.uni-magdeburg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Kalinski
authors.forename: Sabine
authors.initials: S
authors.lastname: Krueger
authors.forename: Saadettin
authors.initials: S
authors.lastname: Sel
authors.forename: Kerstin
authors.initials: K
authors.lastname: Werner
authors.forename: Martin
authors.initials: M
authors.lastname: Röpke
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
mesh_terms: 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
chemical_list: D053583:Interleukin-1beta; D042461:Vascular Endothelial Growth Factor A; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human