TY - JOUR
T1 - Scatter factor expression and regulation in human glial tumors
AU - Rosen, Eliot M.
AU - Laterra, John
AU - Joseph, Ansamma
AU - Jin, Liang
AU - Fuchs, Alexander
AU - Way, Dennis
AU - Witte, Marlys
AU - Weinand, Martin
AU - Goldberg, Itzhak D.
PY - 1996
Y1 - 1996
N2 - Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a cytokine that induces cell motility in vitro and angiogenesis in vivo. SF appears to be a determinant of the malignant phenotype in certain systemic cancers. We detected SF in extracts prepared from human gliomas, with the highest levels found in malignant tumors. Human glioblastoma cells expressed both SF and its receptor (c-met protein) in vivo, as demonstrated by immunohistochemistry. Consistent with these observations, we found moderate to high levels of production of immunoreactive and biologically active SF by cultured human glioblastoma cells (3 of 8 lines) and by neural microvascular endothelial cells (NMVEC) (3 of 3 lines). SF stimulated the proliferation of glioblastoma and NMVEC cell lines by paracrine or autocrine mechanisms. Conditioned medium (CM) from both glioblastoma and NMVEC cells contained SF- inducing factor (SF-IF) activity, defined by its ability to stimulate SF production in an indicator cell line (MRC5 human fibroblasts). This activity consisted of a high-molecular-weight (> 30 kDa), heat-sensitive component and a low-molecular weight (< 30 kDa), heat-stable component. Furthermore, glioblastoma CM stimulated NMVEC SF production, and NMVEC CM stimulated glioblastoma cell SF production, by 3- to 6-fold in each case. Our findings demonstrate that SF-dependent interactions between glioma cells, and between glioma cells and endothelium, can contribute to the heterogeneous proliferative and angiogenic phenotypes of malignant gliomas in vivo.
AB - Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a cytokine that induces cell motility in vitro and angiogenesis in vivo. SF appears to be a determinant of the malignant phenotype in certain systemic cancers. We detected SF in extracts prepared from human gliomas, with the highest levels found in malignant tumors. Human glioblastoma cells expressed both SF and its receptor (c-met protein) in vivo, as demonstrated by immunohistochemistry. Consistent with these observations, we found moderate to high levels of production of immunoreactive and biologically active SF by cultured human glioblastoma cells (3 of 8 lines) and by neural microvascular endothelial cells (NMVEC) (3 of 3 lines). SF stimulated the proliferation of glioblastoma and NMVEC cell lines by paracrine or autocrine mechanisms. Conditioned medium (CM) from both glioblastoma and NMVEC cells contained SF- inducing factor (SF-IF) activity, defined by its ability to stimulate SF production in an indicator cell line (MRC5 human fibroblasts). This activity consisted of a high-molecular-weight (> 30 kDa), heat-sensitive component and a low-molecular weight (< 30 kDa), heat-stable component. Furthermore, glioblastoma CM stimulated NMVEC SF production, and NMVEC CM stimulated glioblastoma cell SF production, by 3- to 6-fold in each case. Our findings demonstrate that SF-dependent interactions between glioma cells, and between glioma cells and endothelium, can contribute to the heterogeneous proliferative and angiogenic phenotypes of malignant gliomas in vivo.
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U2 - 10.1002/(SICI)1097-0215(19960717)67:2<248::AID-IJC16>3.0.CO;2-7
DO - 10.1002/(SICI)1097-0215(19960717)67:2<248::AID-IJC16>3.0.CO;2-7
M3 - Article
C2 - 8760595
AN - SCOPUS:0029830062
SN - 0020-7136
VL - 67
SP - 248
EP - 255
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -