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Expression
and Functional Significance of Vascular Endothelial Growth Factor Receptors
in Human Tumor Cells |
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Christel Herold-Mende,
Hans-Herbert Steiner, Thomas Andl, Daniela Riede, Annette Buttler, Christoph
Reisser, Norbert E. Fusenig, and Margareta M. Mueller |
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Molecular
Biology Laboratory, Department of Neurosurgery (CH-M, H-HS, DR, AB), and
Department of Head and Neck Surgery (CH-M, CR), University of Heidelberg,
and Division of Differentiation and Carcinogenesis, German Cancer Research
Centre (DKFZ), Heidelberg, Germany; and Department of Dermatology (TA),
University of Pennsylvania, Philadelphia, Pennsylvania |
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SUMMARY: Vascular endothelial
growth factor (VEGF) is one of the key factors in tumor neoangiogenesis,
acting through its receptors KDR (VEGFR-2) and flt-1 (VEGFR-1) expressed
on endothelial cells. Our data demonstrate that VEGFR-1 and to a lesser
extent VEGFR-2 are expressed in a number of human tumor tissues and derived
cells in culture. VEGFR-1 protein is expressed in 26 of 42 glioma tissues,
22 of which show a coexpression of VEGFR-1 with VEGFR-2; 1 glioma tissue
expresses exclusively VEGFR-2. In the derived glioma cell cultures, we found
VEGFR-1 mRNA expression in 6 of 11 cultures, with one coexpressing VEGFR-1
and VEGFR-2. Of four established glioma cell lines, two expressed VEGFR-1.
In addition VEGFR-1 protein expression was demonstrated in 30 of 37 tumor
tissues of squamous cell carcinomas of the head and neck, with VEGFR-2 coexpression
in 15 tissues and an expression of VEGFR-2 alone in 1 tissue. Derived tumor
cell cultures showed mRNA expression of VEGFR-1 alone in seven of seven
cases. Established melanoma cell lines expressed VEGFR-1 mRNA in four of
five lines, with VEGFR-2 coexpression in two lines. Concerning the functional
significance of VEGF receptor expression, VEGF treatment of VEGFR-1-expressing
tumor cells induced the inhibition of cell proliferation by 25 to 55%
and the inhibition of tumor cell migration by 29 to 55%. Thus our data
indicate that the coexpression of VEGF and VEGFR-1 in tumor cells could
have an inhibitory effect on tumor cell proliferation and migration, a mechanism
possibly induced as a response to a deficiency in nutrient and oxygen supply. |
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