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Differential expression of VEGF‐A and angiopoietins in cartilage tumors and regulation by interleukin‐1β
Author(s) -
Kalinski Thomas,
Krueger Sabine,
Sel Saadettin,
Werner Kerstin,
Ropke Martin,
Roessner Albert
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21848
Subject(s) - vascular endothelial growth factor , angiogenesis , angiopoietin , immunohistochemistry , western blot , reverse transcription polymerase chain reaction , medicine , cartilage , cancer research , pathology , endocrinology , messenger rna , vegf receptors , biology , anatomy , gene , biochemistry
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)‐1β has been found to be an indispensable factor in angiogenic signaling, we further analyzed the effect of IL‐1β 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‐1β regulated VEGF‐A and Ang‐1 expressions in a dose‐dependent manner. Whereas low IL‐1β concentrations increased VEGF‐A and Ang‐1 transcription, high IL‐1β concentrations had the opposite effect. IL‐1β did not activate Ang‐2 expression. CONCLUSIONS Angiogenic signaling in cartilage tumors is variable and at least partly regulable by IL‐1β. The findings are of therapeutic relevance, either as a desired effect or a side effect in medical treatment. Cancer 2006. © 2006 American Cancer Society.