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Open AccessJournal ArticleDOI

Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development.

TLDR
The results suggest that FLT4 is a marker for lymphatic vessels and some high endothelial venules in human adult tissues, and support the theory on the venous origin of lymphatic Vessels.
Abstract
We have recently cloned the human fms-like tyrosine kinase 4 gene FLT4, whose protein product is related to two vascular endothelial growth factor receptors FLT1 and KDR/FLK1. Here the expression of FLT4 has been analyzed by in situ hybridization during mouse embryogenesis and in adult human tissues. The FLT4 mRNA signals first became detectable in the angioblasts of head mesenchyme, the cardinal vein, and extraembryonally in the allantois of 8.5-day postcoitus (p.c.) embryos. In 12.5-day p.c. embryos, the FLT4 signal decorated developing venous and presumptive lymphatic endothelia, but arterial endothelia were negative. During later stages of development, FLT4 mRNA became restricted to vascular plexuses devoid of red cells, representing developing lymphatic vessels. Only the lymphatic endothelia and some high endothelial venules expressed FLT4 mRNA in adult human tissues. Increased expression occurred in lymphatic sinuses in metastatic lymph nodes and in lymphangioma. Our results suggest that FLT4 is a marker for lymphatic vessels and some high endothelial venules in human adult tissues. They also support the theory on the venous origin of lymphatic vessels.

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The biology of vascular endothelial growth factor

TL;DR: The establishment of a vascular supply is required for organ development and differentiation as well as for tissue repair and reproductive functions in the adult.
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Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium

TL;DR: It is reported that Flt-1 is essential for the organization of embryonic vasculature, but is not essential for endothelial cell differentiation, and it is suggested that the FlT-1 signalling pathway may regulate normal endothelium cell-cell or cell-matrix interactions during vascular development.
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Role of the Vascular Endothelial Growth Factor Pathway in Tumor Growth and Angiogenesis

TL;DR: Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.
Journal ArticleDOI

A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.

TL;DR: VEGF‐C is a novel regulator of endothelia, and its effects may extend beyond the lymphatic system, where Flt4 is expressed.
Journal ArticleDOI

Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis

TL;DR: The occurrence and biological significance of intratumoral lymphangiogenesis within human breast cancers after orthotopic transplantation onto nude mice are established and VEGF-C is identified as a molecular link between tumor lymphang iogenesis and metastasis.
References
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Journal ArticleDOI

The fms-Like Tyrosine Kinase, a Receptor for Vascular Endothelial Growth Factor

TL;DR: Findings show that flt encodes a receptor for VEGF-VPF, a factor that induces vascular permeability when injected in the guinea pig skin and stimulates endothelial cell proliferation.
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High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis.

TL;DR: Investigation of flk-1 receptor tyrosine kinase mRNA expression by in situ hybridization analysis revealed specific association with endothelial cells at all stages of mouse development, suggesting a major role of this ligand-receptor signaling system in vasculogenesis and angiogenesis.
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Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor

TL;DR: The KDR receptor tyrosine kinase shares structural similarities with a recently reported receptor for VEGF, flt, in a manner reminiscent of the similarities between the alpha and beta forms of the PDGF receptors.
Journal ArticleDOI

Monoclonal antibodies against recombinant parts of the ki-67 antigen (mib 1 and mib 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections

TL;DR: The assessment of cell kinetics through the detection of Ki‐67 antigen is now possible on archival material collected in histopathology departments all over the world because this new method is highly reproducible, easy to perform at low cost, and no additional technical skill is needed after microwave treatment.
Journal Article

The role of angiogenesis in tumor growth.

TL;DR: Experimental and clinical evidence is here assembled in support of the concept that the development of a solid tumor progresses from a prevascular phase to a vascular phase, and indicates that for most tumors, the switch to the angiogenic phenotype depends upon the outcome of a balance betweenAngiogenic stimulators and angiogenesis inhibitors.
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