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

Abstract

Tumor angiogenesis depends on the vascular endothelial growth factor (VEGF), which exists in multiple splicing isoforms, including the most abundant VEGF165 and VEGF121. 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 VEGF165 and VEGF121 in human cancer and their influence on tumor growth and vascularization. We measured the expression levels of VEGF165 and VEGF121 in human colorectal cancer and found that VEGF121 was more expressed than VEGF165, particularly in patients with extensive lymph node infiltration. Overexpressing either VEGF165 or VEGF121 in a cancer mouse model, we observed that the former decreased, whereas the latter increased tumor growth. In both clinical and experimental tumors, VEGF165 expression resulted in the recruitment of NEMs, paralleled by maturation of the tumor vascular network. Finally, hypoxia induced a shift toward the VEGF165 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.

<p>Delivery luteolin with folacin-modified nanoparticle for glioma therapy</p>

“…Tumor neovascularization is inseparable of tumor growth, infiltration and metastasis. [38][39][40] In this study, the effect of luteolin on tumor angiogenesis was evaluated by detecting the expression of CD31. It was found that in the two control groups of saline and blank microparticles, the number of neovascular microvessels was 67.8 and 66.4, respectively, while in the three experimental groups of free luteolin, luteolin nanometers and folic acid-modified nanomedicine, the number of microvessels in neonatal tumors was significantly reduced, which were 45.2, 27 and 12.0, respectively, which suggests that luteolin has an important role in inhibiting tumor angiogenesis.…”

Distinct Vegfa isoforms control endothelial cell proliferation through PI3 kinase signalling mediated regulation of cdkn1a/p21

“…This setting allowed us to determine the unique effects of ECM binding Vegfa isoforms on EC behaviors during embryogenesis. Previous studies in developing mice (Ruhrberg et al, 2002; Stalmans et al, 2002), disease settings (Brash et al, 2019; Cheng et al, 1997; Guo et al, 2001; Kazemi et al, 2016) and in cultured ECs (Chen et al, 2010; Delcombel et al, 2013; Fearnley et al, 2016; Herve et al, 2005; Park et al, 1993; Shiying et al, 2017) carefully investigated the effects of the different VEGF isoforms on cellular behaviors (for review see (Peach et al, 2018; Woolard et al, 2009)). Some studies suggested that there are no differences in the ability of various VEGFA isoforms to support EC proliferation (Ruhrberg et al, 2002), while others showed that ECs cultured on ECM derived from cells expressing VEGF189 or VEGF206 proliferated more strongly than those cultured in the presence of VEGF165 (Park et al, 1993).…”

Anti‐Flt1 peptide and cyanine‐conjugated gold nanoparticles for the concurrent antiangiogenic and endothelial cell proton treatment

“…Moreover, Flt1@AuNP‐Cy5.5 nanocomplexes demonstrated direct binding affinity with other ligands of VEGFR‐1, such as VEGF 165 , PIGF, and VEGFb. VEGF 165 binds to specific VEGFR‐1 receptors as a ligand peptide, resulting in angiogenesis and vascular diseases in cancer or the retina of the eye . Efficient binding of Flt1@AuNP‐Cy5.5 with VEGFR ligands suggests the potential role of VEGF inhibitors, such as Ranibizumab and VEGFR‐1 decoy receptors, in inhibiting the VEGF‐mediated activation of VEGFRs.…”