Differential expression of VEGF-A and angiopoietins in cartilage tumors and regulation by interleukin-1beta.
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)-1beta has been found to be an indispensable factor in angiogenic signaling, we further analyzed the effect of IL-1beta 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-1beta regulated VEGF-A and Ang-1 expressions in a dose-dependent manner. Whereas low IL-1beta concentrations increased VEGF-A and Ang-1 transcription, high IL-1beta concentrations had the opposite effect. IL-1beta did not activate Ang-2 expression.


CONCLUSIONS
Angiogenic signaling in cartilage tumors is variable and at least partly regulable by IL-1beta. The findings are of therapeutic relevance, either as a desired effect or a side effect in medical treatment.
Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany. kalinski@medizin.uni-magdeburg.de
Thomas
T
Kalinski
Sabine
S
Krueger
Saadettin
S
Sel
Kerstin
K
Werner
Martin
M
Ropke
Albert
A
Roessner
D000328:Adult; D000368:Aged; D042683:Angiopoietin-1 / Q000235:genetics*; D042702:Angiopoietin-2 / Q000235:genetics*; D045744:Cell Line, Tumor; D002812:Chondroma / Q000098:blood supply / Q000378:metabolism*; D002813:Chondrosarcoma / Q000098:blood supply / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics*
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D007375:Interleukin-1; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A