Properties of Two VEGF Receptors, Flt‐1 and KDR, in Signal Transduction<sup>a</sup>

Sato, Yasufumi; Kanno, Satoshi; Oda, Noriichi; Abé, Mayumi; Ito, Mikito; Shitara, Kenya; Shibuya, Masabumi

doi:10.1111/j.1749-6632.2000.tb06314.x

Cited by 120 publications

(83 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This family consists of VEGFR-1 and VEGFR-2, which mediate growth factor signals for blood vascular endothelial cells, and VEGFR-3, which mainly regulates lymphatic endothelial cells. Expression of VEGFR-1 and VEGFR-2 is mainly restricted to the vascular endothelium [101].…”

Section: Vascular Endothelial Growth Factormentioning

confidence: 99%

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

et al. 2007

View full text Add to dashboard Cite

Esophageal cancer is a highly aggressive disease and is the seventh most common cause of cancer-related death in the western world. Worldwide, it ranks as the sixth most frequent cause of cancer death. Despite advances in surgical techniques and treatment, the prognosis of esophageal cancer remains poor, with very few longterm survivors. The need for novel strategies to detect esophageal cancer earlier and to improve current therapy is urgent.It is well established that growth factors and growth factor receptor-mediated signaling pathways are important components of the transformation process in many forms of cancer, including esophageal cancer. With the recent advances in drug development, there are emerging possibilities to use growth factor signal transduction pathways in targeted therapy. This review provides a summary of the role of growth factors and their receptors in esophageal cancer and discusses their potential roles as biomarkers and as targets in therapy.

show abstract

Section: Vascular Endothelial Growth Factormentioning

confidence: 99%

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

et al. 2007

View full text Add to dashboard Cite

show abstract

“…42 We hypothesize that the alteration in pericyte coverage may involve VEGF up-regulation and HIF-1␣ regulatory mechanisms. In this experiment, with immunohistochemical technique, we found VEGF constitutively expressed in various cells in the stria vascularis, including both vascular cells (pericytes and ECs) and nonvascular cells such as MCs in the control mice ( Figure 7A; V/arrow, MC/arrow).…”

Section: Noise Induced Up-regulation Of Vegf Associated With Hif-1␣ Amentioning

confidence: 99%

“…We found that neither sodium butyrate nor SU1498 had ototoxicities in all six tested mice in the two treated groups (n ϭ 3). To determine whether dosage of SU1498 was sufficient to inhibit VEGF activity, the activity of focal adhesion kinase, a widely expressed cytoplasmic protein tyrosine kinase involved in VEGF-mediated signal transduction 42 has been examined in the cochlear lateral wall tissues. We found that immunoreactivity for focal adhesion kinase in the noise-exposed mice was high compared with the nonnoise exposed mice.…”

Section: Su1498 and Sodium Butyrate Treatmentsmentioning

confidence: 99%

Cochlear Pericyte Responses to Acoustic Trauma and the Involvement of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor

Shi

2009

The American Journal of Pathology

View full text Add to dashboard Cite

This study explored the effect of acoustic trauma on cochlear pericytes. Transmission electron microscopy revealed that pericytes on capillaries of the stria vascularis were closely associated with the endothelium in both control guinea pigs and mice. Pericyte foot processes were tightly positioned adjacent to endothelial cells. Exposure to wide-band noise at a level of 120 dB for 3 hours per day for 2 consecutive days produced a significant hearing threshold shift and structurally damaged blood vessels in the stria vascularis. Additionally, the serum protein, IgG, was observed to leak from capillaries of the stria vascularis, and pericytes lost their tight association with endothelial cells. Levels of the pericyte structural protein, desmin, substantially increased after noise exposure in both guinea pigs and mice with a corresponding increase in pericyte coverage of vessels. Increased expression levels of desmin were associated with the induction of hypoxia inducible factor (HIF)-1␣ and the up-regulation of vascular endothelial growth factor (VEGF). Inhibition of HIF-1␣ activity caused a decrease in VEGF expression levels in stria vascularis vessels. Blockade of VEGF activity with SU1498, a VEGF receptor inhibitor, significantly attenuated the expression of desmin in pericytes. These data demonstrate that cochlear pericytes are markedly affected by acoustic trauma and display an abnormal morphology. HIF-1␣ activation and VEGF up-regulation are important factors for the alteration of the pericyte structural protein desmin. (Am J Pathol

show abstract

“…VEGF displays these broad vascular functions via binding and activation of its specific receptors, VEGFR-1 and VEGFR-2, mainly expressed in vascular endothelial cells, although other cell types may also express these receptors (5)(6)(7)(8). Abundant experimental data demonstrate that VEGFR-2 is the primary functional receptor that transduces both angiogenic and vascular permeability signals whereas VEGFR-1 may function as a decoy receptor (9,10). It should be emphasized that, under physiological and pathological conditions, VEGFR-2 is expressed not only in angiogenic vessels, but also in quiescent vasculatures in various tissues (11).…”

mentioning

confidence: 99%

Anti-VEGF– and anti-VEGF receptor–induced vascular alteration in mouse healthy tissues

Yang

Zhang

Cao

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

View full text Add to dashboard Cite

Systemic therapy with anti-VEGF drugs such as bevacizumab is widely used for treatment of human patients with various solid tumors. However, systemic impacts of such drugs in host healthy vasculatures remain poorly understood. Here, we show that, in mice, systemic delivery of an anti-VEGF or an anti–VEGF receptor (VEGFR)-2 neutralizing antibody caused global vascular regression. Among all examined tissues, vasculatures in endocrine glands, intestinal villi, and uterus are the most affected in response to VEGF or VEGFR-2 blockades. Thyroid vascular fenestrations were virtually completely blocked by VEGF blockade, leading to marked accumulation of intraendothelial caveolae vesicles. VEGF blockade markedly increased thyroid endothelial cell apoptosis, and withdrawal of anti-VEGF resulted in full recovery of vascular density and architecture after 14 d. Prolonged anti-VEGF treatment resulted in a significant decrease of the circulating level of the predominant thyroid hormone free thyroxine, but not the minimal isoform of triiodothyronine, suggesting that chronic anti-VEGF treatment impairs thyroid functions. Conversely, VEGFR-1–specific blockade produced virtually no obvious phenotypes. These findings provide structural and functional bases of anti-VEGF–specific drug-induced side effects in relation to vascular changes in healthy tissues. Understanding anti-VEGF drug-induced vascular alterations in healthy tissues is crucial to minimize and even to avoid adverse effects produced by currently used anti-VEGF–specific drugs.

show abstract

Properties of Two VEGF Receptors, Flt‐1 and KDR, in Signal Transduction^a

Cited by 120 publications

References 23 publications

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

Cochlear Pericyte Responses to Acoustic Trauma and the Involvement of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor

Anti-VEGF– and anti-VEGF receptor–induced vascular alteration in mouse healthy tissues

Contact Info

Product

Resources

About

Properties of Two VEGF Receptors, Flt‐1 and KDR, in Signal Transductiona

Cited by 120 publications

References 23 publications

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

Cochlear Pericyte Responses to Acoustic Trauma and the Involvement of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor

Anti-VEGF– and anti-VEGF receptor–induced vascular alteration in mouse healthy tissues

Contact Info

Product

Resources

About

Properties of Two VEGF Receptors, Flt‐1 and KDR, in Signal Transduction^a