Tubulogenesis by microvascular endothelial cells is mediated by vascular endothelial growth factor (VEGF) in renal cell carcinoma.
OBJECTIVE
To investigate the role of vascular endothelial growth factor (VEGF) in tumour angiogenesis in renal cell carcinoma (RCC).


METHODS
The expression of VEGF was examined in tissue samples from 25 patients with RCC using the reverse-transcriptase polymerase chain reaction (RT-PCR). Cellular localization of VEGF was studied in normal kidney and RCC tissues. Tube formation by human omental microvascular endothelial (HOME) cells co-cultured with A498 RCC cells was quantified in a three-dimensional collagen gel using computer-image analysis.


RESULTS
RT-PCR detected VEGF m-RNA in tissue from 20 of 25 patients with RCC. An immunohistochemical study revealed that VEGF was primarily localized in the cytosol of normal renal tubule cells and RCC cells. Tube formation by HOME cells was increased in the presence of A498 cells overexpressing VEGF mRNA, induced by exogenous VEGF in a dose-dependent manner and completely inhibited by an anti-VEGF antibody.


CONCLUSIONS
VEGF, which is produced and released from RCC cells, may elicit tumour angiogenesis by inducing microvessel tubulogenesis in patients with RCC. The co-culture system may be useful for screening inhibitors of tumour angiogenesis in RCC.
Nakagawa
M
M
Department of Urology, Oita Medical University, Japan.
Emoto
A
A
Hanada
T
T
Nasu
N
N
Nomura
Y
Y
D015152:Blotting, Northern; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors