Xenografts of human solid tumors frequently express cellular-associated isoform of vascular endothelial growth factor (VEGF) 189.

Okamoto, Koichi; Oshika, Y; Fukushima, Yasushi; Ohnishi, Yasuyuki; Tokunaga, Tetsuji; Tomii, Yasushi; Kijima, Hiroshi; Yamazaki, Hitoshi; Ueyama, Y; Tamaoki, Norikazu; Nakumura, Morihiko

doi:10.3892/or.6.6.1201

Cited by 9 publications

(12 citation statements)

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“…This correlates with results from Pat D'Amore's team, which showed that the basic ECM binding VEGF isoforms are necessary in retinal vascular development to allow vessels to branch out from the center of the retina (36). It has been shown that VEGF 189 expression is up-regulated more than other VEGF isoforms in esophageal xenografts (37) and by some types of tumor cells, for example, in human colon and in non-small-cell lung cancer (38). In these cases, VEGF 189 in the tumor ECM or associated with the cell surface could be a support for endothelial cell migration into the tumor mass.…”

Section: Discussionsupporting

confidence: 82%

Extracellular matrix‐bound vascular endothelial growth factor promotes endothelial cell adhesion, migration, and survival through integrin ligation

2003

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Vascular endothelial growth factor (VEGF), a major factor mediating endothelial cell survival, migration, and proliferation during angiogenesis, is expressed as five splice variants (121, 145, 165, 189, and 206 aminoacids) encoded by a single gene. Although the three shorter isoforms are mainly diffusible, the two longer ones are sequestered in cell membranes after secretion. However, their potential role as true components of the extracellular matrix has not been investigated. We determined that endothelial cells could adhere and spread on VEGF189 and VEGF165, but not on VEGF121. Adhesion was mediated by the alpha3beta1 and alpha(v)beta3 integrins and other alpha(v) integrins but not by the cognate VEGF receptors. Cells migrated on VEGF165 and VEGF189 and displayed a stellate morphology with numerous lamellopodia and FAK staining but no actin stress fibers. Tumstatin, an antiangiogenic peptide that interacts with the alpha(v)beta3 integrin, could inhibit adhesion on VEGF, and this effect was potentiated by anti-alpha(v)beta3 blocking antibody. Immobilized VEGF almost totally abolished endothelial cell apoptosis through interactions with integrins. The inhibition of alpha(v)beta3 engagement with immobilized VEGF by tumstatin inhibited most of its survival activity. We have thus determined a new VEGF receptor-independent role for immobilized VEGF in supporting cell adhesion and survival through interactions with integrins.

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Section: Discussionsupporting

confidence: 82%

Extracellular matrix‐bound vascular endothelial growth factor promotes endothelial cell adhesion, migration, and survival through integrin ligation

2003

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“…Cells expressing VEGF-A usually express all the isoforms simultaneously [21], however, there are specific biases to the isoforms of VEGF-A expressed. For instance, VEGF-A isoform expression varies during blastocyst implantation [22,23], embryogenesis [7] as well as in the normal adult [24] and may also account for differences in the behaviour of benign and malignant tumours [25][26][27][28]. In this study, the VEGFA 120&164 isoforms are most abundant in the wild-type lens.…”

Section: Discussionmentioning

confidence: 93%

Unique vascular phenotypes following over-expression of individual VEGFA isoforms from the developing lens

et al. 2006

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Formation of a correctly organised vasculature and subsequently embryonic survival is critically dependent on the dosage and site-specific expression of VEGF. Murine VEGF exists in three common isoforms (viz. 120, 164 and 188 amino acids) having different organ specific distribution levels. Gene knock-in studies show that expression of any of the individual isoforms of VEGF extends survival until birth, although each is associated with distinct organ-specific abnormalities. Comparison of the effects of VEGF isoform expression is complicated by the general lethality of mis-expression, in addition to cumulative effects of adjacent tissues from the inappropriately patterned vasculature. Here we investigate the effects of over-expression of individual VEGFA isoforms from the lens-specific alphaA-Crystallin promoter and characterise their effects on the vessel morphology of the hyaloid and developing retinal vasculature. Since the hyaloid vasculature is an anatomically distinct, transient vasculature of the eye, comprising 3 cell types (endothelium, pericytes and macrophages) it is possible to more readily interpret the role of individual VEGF-A isoforms in vascular pattern formation in this model. The severity of the vascular phenotype, characterised by a hyperplastic hyaloid at E13.5 and subsequently retinal vascular patterning and ocular defects, is most severe in transgenics over-expressing the more diffusible forms of VEGFA (120 and 164), whereas in VEGFA(188) transgenics the hyaloid vascular defects partially resolve post-natally. The results of this study indicate that individual isoforms of VEGFA induce distinct vascular phenotypes in the eye during embryonic development and that their relative doses provide instructive cues for vascular patterning.

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“…The C-terminal propeptide significantly enhanced this interaction through the removal of this propeptide from full-length VEGF-D. The removal of either the N- or C-terminal propeptide was required for VEGF-D binding to VEGFR-2/VEGFR-3 and formation of heterodimers, which have recently been shown to positively regulate angiogenic and lymphangiogenic sprouting (28,29). In contrast, the removal of both propeptides was required for high rates of lymph node metastasis.…”

Section: Discussionmentioning

confidence: 99%

Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D

Zhu

Zhou

et al. 2016

Oncology Reports

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In our previous studies, sulfatase 2 (Sulf2) was found to upregulate vascular endothelial growth factor-D (VEGF-D) expression in breast cancer. As VEGF-D plays an important role in lymphangiogenesis, we hypothesized that Sulf2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. To evaluate the functions of Sulf2 on lymphangiogenesis in breast cancer, proliferation, apoptosis, cell cycle, cell mobility and tube-formation of lymphatic endothelial cells (LECs) were measured in vitro. Lymphangiogenesis in nude mouse ears and breast cancer xenografts were examined in vivo. Furthermore, the expression levels of related signaling pathway genes were screened and verified in LECs. We found that Sulf2 significantly increased the mobility and tube formation of the LECs, inhibited cisplatin-induced LEC apoptosis, but had no effect on cell proliferation and the cell cycle. Moreover, recombinant Sulf2 (rSulf2) combined with VEGF-D further promoted the proliferation, cell cycle, mobility and tube-like structure formation in the LECs, and at the same time inhibited cisplatin-induced apoptosis especially in the late stage. Sulf2 also significantly increased the density of lymphatic vessels in mouse ears and breast cancer xenografts in vivo. AKT1 was also shown to be upregulated and activated by Sulf2. Our results confirmed that Sulf2 facilitated lymphangiogenesis in breast cancer cells by regulating VEGF-D and that the AKT1-related signaling pathway was involved.

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Xenografts of human solid tumors frequently express cellular-associated isoform of vascular endothelial growth factor (VEGF) 189.

Cited by 9 publications

References 0 publications

Extracellular matrix‐bound vascular endothelial growth factor promotes endothelial cell adhesion, migration, and survival through integrin ligation

Extracellular matrix‐bound vascular endothelial growth factor promotes endothelial cell adhesion, migration, and survival through integrin ligation

Unique vascular phenotypes following over-expression of individual VEGFA isoforms from the developing lens

Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D

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