Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR.
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Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR. / Graeven, U; Fiedler, W; Karpinski, S; Ergün, S; Kilic, Nerbil; Rodeck, U; Schmiegel, W; Hossfeld, D K.
In: J CANCER RES CLIN, Vol. 125, No. 11, 11, 1999, p. 621-629.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Melanoma-associated expression of vascular endothelial growth factor and its receptors FLT-1 and KDR.
AU - Graeven, U
AU - Fiedler, W
AU - Karpinski, S
AU - Ergün, S
AU - Kilic, Nerbil
AU - Rodeck, U
AU - Schmiegel, W
AU - Hossfeld, D K
PY - 1999
Y1 - 1999
N2 - The expression patterns of vascular endothelial growth factor (VEGF) and its two receptors, flt-1 and KDR, were assessed in normal human melanocytes, transformed melanocytes expressing the simian virus 40 Tgene (SV40T), and melanoma cells derived from primary and metastatic lesions. Constitutive expression of VEGF, flt-1, and KDR mRNA and proteins was observed in the majority of primary and metastatic melanoma cell lines, and in SV40T-transformed melanocytes. VEGF expression in melanoma cell lines was further enhanced by exogenous growth factors including insulin and fetal calf serum. By contrast, neonatal melanocytes did not express VEGF or VEGF receptors and VEGF expression could not be induced by exogenous growth factors. Exogenous VEGF had no significant effects on melanoma cell proliferation or on production of a transcriptional target for VEGF, urokinase-type plasminogen activator. Down-regulation of VEGF expression in the metastatic melanoma cell line WM164 through transfection of a VEGF antisense construct similarly did not affect proliferation of the transfected cells in the presence or absence of exogenous VEGF. In summary, coexpression of VEGF and its receptors is a tumor-associated phenomenon in melanoma development. However VEGF production does not support autocrine proliferation of the melanoma cell lines tested.
AB - The expression patterns of vascular endothelial growth factor (VEGF) and its two receptors, flt-1 and KDR, were assessed in normal human melanocytes, transformed melanocytes expressing the simian virus 40 Tgene (SV40T), and melanoma cells derived from primary and metastatic lesions. Constitutive expression of VEGF, flt-1, and KDR mRNA and proteins was observed in the majority of primary and metastatic melanoma cell lines, and in SV40T-transformed melanocytes. VEGF expression in melanoma cell lines was further enhanced by exogenous growth factors including insulin and fetal calf serum. By contrast, neonatal melanocytes did not express VEGF or VEGF receptors and VEGF expression could not be induced by exogenous growth factors. Exogenous VEGF had no significant effects on melanoma cell proliferation or on production of a transcriptional target for VEGF, urokinase-type plasminogen activator. Down-regulation of VEGF expression in the metastatic melanoma cell line WM164 through transfection of a VEGF antisense construct similarly did not affect proliferation of the transfected cells in the presence or absence of exogenous VEGF. In summary, coexpression of VEGF and its receptors is a tumor-associated phenomenon in melanoma development. However VEGF production does not support autocrine proliferation of the melanoma cell lines tested.
M3 - SCORING: Zeitschriftenaufsatz
VL - 125
SP - 621
EP - 629
JO - J CANCER RES CLIN
JF - J CANCER RES CLIN
SN - 0171-5216
IS - 11
M1 - 11
ER -