Endothelial receptor tyrosine kinases involved in angiogenesis.

Mustonen, Tuija; Alitalo, Kari

doi:10.1083/jcb.129.4.895

Cited by 486 publications

(302 citation statements)

References 38 publications

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“…Angiogenic signals trigger complex changes in endothelial cells and extracellular matrix that result in remodelling, migration, and proliferation of pre-existing endothelium. The process begins with the proliferation of proximal endothelial cells that form capillary branches, with vessel lumen forming through anastomotic connections between capillary tips (Mustonen and Alitalo, 1995;Risau, 1997). Angiogenesis also depends on adhesive interactions between vascular cells of which multiple adhesion molecules are involved, such as avb3, avb5, a5b1, and a2b1 integrins; PECAM-1; and VE-cadherin (Heimark et al, 1990;Lampugnani et al, 1991Lampugnani et al, , 1992Brooks, 1996).…”

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confidence: 99%

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

et al. 2007

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Angiogenesis and post-natal vasculogenesis are two processes involved in the formation of new vessels, and both are essential for tumour growth and metastases. We isolated endothelial cells from human blood mononuclear cells by selective culture. These blood outgrowth cells expressed endothelial cell markers and responded correctly to functional assays. To evaluate the potential of blood outgrowth endothelial cells (BOECs) to construct functional vessels in vivo, NOD-SCID mice were implanted with Lewis lung carcinoma cells subcutaneously (s.c.). Blood outgrowth endothelial cells were then injected through the tail vein. Initial distribution of these cells occurred throughout the lung, liver, spleen, and tumour vessels, but they were only found in the spleen, liver, and tumour tissue 48 h after injection. By day 24, they were mainly found in the tumour vasculature. Tumour vessel counts were also increased in mice receiving BOEC injections as compared to saline injections. We engineered BOECs to deliver an angiogenic inhibitor directly to tumour endothelium by transducing them with the gene for human endostatin. These cells maintained an endothelial phenotype and decreased tumour vascularisation and tumour volume in mice. We conclude that BOECs have the potential for tumour-specific delivery of cancer gene therapy.

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confidence: 99%

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

et al. 2007

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“…They are characterized by the presence of 7 immunoglobulin-like domains in the extracellular domain and an intracellular domain with homology to the platelet-derived growth factor receptor (PDGFR) subfamily. 2 Two alternatively spliced isoforms of VEGFR-3 have been reported, 3 though in contrast to VEGFR-1, there is no evidence so far that a naturally occurring soluble receptor form exists for VEGFR-3. 4 The growth of lymphatic vessels is called lymphangiogenesis and occurs after tissue injury, obstruction or damage of lymphatic vessels.…”

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Immunodetection and quantification of vascular endothelial growth factor receptor‐3 in human malignant tumor tissues

Bando

Brokelmann

Toi

et al. 2004

Intl Journal of Cancer

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Vascular endothelial growth factor recpetor-3 (VEGFR-3) and its ligands, vascular endothelial growth factor-C (VEGF-C) and -D (VEGF-D), are the major molecules involved in developmental and pathological lymphangiogenesis. Here we describe for the first time the development of a specific indirect enzyme-linked immunosorbent assay (ELISA) for the quantification of VEGFR-3 in different human cell and tissue lysates. A combination of the goat polyclonal anti-VEGFR-3 antibody and the mouse monoclonal anti-human VEGFR-3 antibody was used. The assay was highly sensitive and reproducible with a detection range of 0.2-25 ng/ ml. The assay was specific for VEGFR-3, with no crossreactivity to VEGFR-1 or VEGFR-2. Complex formation with VEGF-C and VEGF-D had no effect on the sensitivity of the assay. The VEGFR-3 concentration in the lysates of cultured human dermal microvascular endothelial cells was 14-fold higher than in the lysates from human umbilical vein endothelial cells. In human kidney, breast, colon, gastric and lung cancer tissues the protein levels of VEGFR-3 were in the range of 0.6 -16.7 ng/mg protein. Importantly, the level of VEGFR-3 protein detected in the ELISA correlated significantly with the number of VEGFR-3 positive vessels observed in histochemical sections, suggesting that the ELISA assay may be a reliable surrogate of measuring VEGFR-3-positive vessel density. The protein levels of VEGFR-3 in 27 renal cell carcinoma samples had a significant correlation with the levels of VEGF-C (p<0.001), or biological active, free VEGF-A (p<0.0001), but not with VEGFR-1 or total VEGF-A. This assay provides a useful tool for the investigations of the expression levels of VEGFR-3 in physiological and pathological processes, particular in cancer and in lymphangiogenesisrelated disease.

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“…10 Ang1 and Ang2 are also largely specific for the vascular endothelium, because expression of their receptor Tie2 (tunica interna endothelial cell kinase 2) is mainly restricted to endothelial cells. 11 Whilst Ang1 supports endothelial cell survival and promotes endothelium integrity, 12 Ang2 by itself antagonizes Ang1 signaling leading to vessel destabilization and regression; however, in combination with VEGF it stimulates new vessel formation. 13 Besides VEGF and the Angs, there are other factors that stimulate blood vessel formation that have a broader target cell spectrum, such as fibroblast growth factor 2 (FGF2) 14 and cysteine-rich protein 61 (CYR61).…”

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confidence: 99%

Differential regulation of blood vessel formation between standard and delayed bone healing

Lienau

Schmidt‐Bleek

Peters

et al. 2009

Journal Orthopaedic Research

122

120

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Blood vessel formation is a prerequisite for bone healing. In this study, we tested the hypothesis that a delay in bone healing is associated with an altered regulation of blood vessel formation. A tibial osteotomy was performed in two groups of sheep and stabilized with either a rigid external fixator leading to standard healing or with a highly rotationally unstable one leading to delayed healing. At days 4, 7, 9, 11, 14, 21, and 42 after surgery, total RNA was extracted from the callus. Gene expressions of vWF, an endothelial cell marker, and of several molecules related to blood vessel formation were studied by qPCR. Furthermore, histology was performed on fracture hematoma and callus sections. Histologically, the first blood vessels were detected at day 7 in both groups. mRNA expression levels of vWF, Ang1, Ang2, VEGF, CYR61, FGF2, MMP2, and TIMP1 were distinctly lower in the delayed compared to the standard healing group at several time points. Based on differential expression patterns, days 7 and 21 postoperatively were revealed to be essential time points for vascularization of the ovine fracture callus. This work demonstrates for the first time a differential regulation of blood vessel formation between standard and mechanically induced delayed healing in a sheep osteotomy model. ß

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Endothelial receptor tyrosine kinases involved in angiogenesis.

Cited by 486 publications

References 38 publications

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

Immunodetection and quantification of vascular endothelial growth factor receptor‐3 in human malignant tumor tissues

Differential regulation of blood vessel formation between standard and delayed bone healing

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