TY - JOUR
T1 - Membrane ganglioside enrichment lowers the threshold for vascular endothelial cell angiogenic signaling
AU - Liu, Yihui
AU - McCarthy, James
AU - Ladisch, Stephan
PY - 2006/11/1
Y1 - 2006/11/1
N2 - Malignant tumor progression depends on angiogenesis, requiring vascular endothelial cell migration, and proliferation, triggered by tumor-derived vascular endothelial cell growth factor (VEGF). We show that gangliosides, which are actively shed by tumor cells and bind to normal cells in the tumor microenvironment, have the potential to sensitize vascular endothelial cells to respond to subthreshold levels of VEGF: Ganglioside enrichment of human umbilical vein vascular endothelial cells (HUVEC) caused very low, normally barely stimulatory, VEGF concentrations to trigger robust VEGF receptor dimerization and autophosphorylation, as well as activation of downstream signaling pathways, and cell proliferation and migration. Thus, by dramatically lowering the threshold for growth factor activation of contiguous normal stromal cells, shed tumor gangliosides may promote tumor progression by causing these normal cells to become increasingly autonomous from growth factor requirements by a process that we term tumor-induced progression of the microenvironment.
AB - Malignant tumor progression depends on angiogenesis, requiring vascular endothelial cell migration, and proliferation, triggered by tumor-derived vascular endothelial cell growth factor (VEGF). We show that gangliosides, which are actively shed by tumor cells and bind to normal cells in the tumor microenvironment, have the potential to sensitize vascular endothelial cells to respond to subthreshold levels of VEGF: Ganglioside enrichment of human umbilical vein vascular endothelial cells (HUVEC) caused very low, normally barely stimulatory, VEGF concentrations to trigger robust VEGF receptor dimerization and autophosphorylation, as well as activation of downstream signaling pathways, and cell proliferation and migration. Thus, by dramatically lowering the threshold for growth factor activation of contiguous normal stromal cells, shed tumor gangliosides may promote tumor progression by causing these normal cells to become increasingly autonomous from growth factor requirements by a process that we term tumor-induced progression of the microenvironment.
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U2 - 10.1158/0008-5472.CAN-06-1572
DO - 10.1158/0008-5472.CAN-06-1572
M3 - Article
C2 - 17079461
AN - SCOPUS:33751277760
SN - 0008-5472
VL - 66
SP - 10408
EP - 10414
JO - Cancer Research
JF - Cancer Research
IS - 21
ER -