Comparative Analysis of Cyclooxygenase-2, Vascular Endothelial Growth Factor and Microvessel Density in Human Renal Cell Carcinomas
Posted on: Wednesday, 15 September 2004, 06:00 CDT
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Aims: Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) play a role in proliferation, apoptosis, angiogenesis and tumour invasion. In the present study, the expression of COX-2 and VEGF in RCC were analysed and correlated with the micro vessel density (MVD).
Methods: COX-2 and VEGF were analysed by realtime-reverse transcriptase polymerase chain reaction and immuno-histochemistry. The MVD was assessed by CD31 immuno-histochemistry. The expression of COX-2 and VEGF was determined in the renal cell carcinoma cell lines A498 and Caki-1 under short-term hypoxia and in multicellular tumour cell aggregates.
Results: COX-2 was expressed in RCC by tumour epithelia, endothelia and macrophages in cystic tumour regressions and tumour necrosis. COX-2 protein in RCC was not altered in comparison to normal renal tissue. VEGF mRNA was up-regulated in RCC and positively correlated with the MVD. RCC with a high up-regulation of VEGF mRNA showed a minor intracytoplasmic expression of VEGF in tumour cells. The intracytoplasmic VEGF protein expression was negatively correlated with the microvessel density. In RCC with necrosis the MVD was reduced in comparison to RCC without necrosis. A498 RCC cells down-regulated COX-2 and upregulated VEGF under hypoxia. In Caki-1 cells COX-2 expression remained stable whereas VEGF was significantly up-regulated. In multicellular A498 cell aggregates COX-2 and VEGF were up-regulated centrally whereas no gradient was found in Caki-1 cells.
Conclusions: COX-2 and VEGF are potential therapeutic targets because COX-2 and VEGF are expressed in RCC epithelia and associated cell populations such as endothelia and monocytes/ macrophages.
B. HEMMERLEIN, H.-J. RADZUN, M. HEUSER1
Abteilung Pathologie, Georg-August-Universitt Gttingen
1 Urologische Klinik, Georg-August-Universitt Gttingen
Copyright Urban & Fischer Verlag 2004
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