Vascular endothelial growth factor (VEGF) mRNA expression in human tumor models of different histologies.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a polypeptide with specific effects on endothelial cell growth and blood vessel permeability. Recent studies demonstrated a key role for VEGF in tumor neovascularization, which is a prerequisite for tumor proliferation and metastasis.


METHODS
We studied the expression of VEGF mRNA in a panel of 65 different human tumor xenografts of various histologies using Northern and slot blot analyses. Analyis of vessel density was performed morphologically and after immunohistochemical staining of endothelial cells.


RESULTS
High expression levels were observed in 22/65 tumors. In melanoma, colorectal, gastric, breast and lung cancers only single tumors showed strong expression signals, whereas 7/10 renal cell carcinoma (RCC) xenografts demonstrated high levels of VEGF mRNA. Vessel density analysis revealed a clear correlation of VEGF mRNA expression with vascularization in RCC (p = 0.0048). Patient survival time was compared for tumors showing high versus low expression values. The overall 5-year survival rate was significantly lower for patients with high expression of VEGF mRNA (p = 0.0306).


CONCLUSIONS
These data support the hypothesis that tumor cells of various histologies secrete VEGF, which acts as a paracrine factor to induce endothelial cell proliferation and vessel formation and mediates tumor progression.
Berger
D P
DP
Department of Internal Medicine I, University of Freiburg, Germany.
Herbstritt
L
L
Dengler
W A
WA
Marmé
D
D
Mertelsmann
R
R
Fiebig
H H
HH
D000818:Animals; D015152:Blotting, Northern; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D015999:Multivariate Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D014183:Transplantation, Heterologous / Q000473:pathology*; 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