Tumor angiogenesis depends on the vascular endothelial growth factor (VEGF), which exists in multiple splicing isoforms, including the most abundant VEGF(165) and VEGF(121). We have previously shown that the differential capacity of these two VEGF isoforms to bind Neuropilin-1 accounts for their diverse ability to recruit Nrp1-expressing monocytes (NEMs), resulting in a different arteriogenic potential. Here we measure the expression of VEGF(165) and VEGF(121) in human cancer and their influence on tumor growth and vascularization. We measured the expression levels of VEGF(165) and VEGF(121) in human colorectal cancer and found that VEGF(121) was more expressed than VEGF(165), particularly in patients with extensive lymph node infiltration. Overexpressing either VEGF(165) or VEGF(121) in a cancer mouse model, we observed that the former decreased, whereas the latter increased tumor growth. In both clinical and experimental tumors, VEGF(165) expression resulted in the recruitment of NEMs, paralleled by maturation of the tumor vascular network. Finally, hypoxia induced a shift toward the VEGF(165) isoform in the central core of human cancers, as well as in various types of cultured cells. These results demonstrate that the two VEGF splicing isoforms are differentially expressed in colorectal cancers, exerting opposite effects on tumor growth and vessel maturation.

VEGF121 and VEGF165 differentially promote vessel maturation and tumor growth in mice and humans

Carrer, A;
2016

Abstract

Tumor angiogenesis depends on the vascular endothelial growth factor (VEGF), which exists in multiple splicing isoforms, including the most abundant VEGF(165) and VEGF(121). We have previously shown that the differential capacity of these two VEGF isoforms to bind Neuropilin-1 accounts for their diverse ability to recruit Nrp1-expressing monocytes (NEMs), resulting in a different arteriogenic potential. Here we measure the expression of VEGF(165) and VEGF(121) in human cancer and their influence on tumor growth and vascularization. We measured the expression levels of VEGF(165) and VEGF(121) in human colorectal cancer and found that VEGF(121) was more expressed than VEGF(165), particularly in patients with extensive lymph node infiltration. Overexpressing either VEGF(165) or VEGF(121) in a cancer mouse model, we observed that the former decreased, whereas the latter increased tumor growth. In both clinical and experimental tumors, VEGF(165) expression resulted in the recruitment of NEMs, paralleled by maturation of the tumor vascular network. Finally, hypoxia induced a shift toward the VEGF(165) isoform in the central core of human cancers, as well as in various types of cultured cells. These results demonstrate that the two VEGF splicing isoforms are differentially expressed in colorectal cancers, exerting opposite effects on tumor growth and vessel maturation.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3455396
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