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. 2010 Nov;1(11):1119-23.
doi: 10.1177/1947601910392987.

Tyrosine Kinase Receptor Flt/VEGFR Family: Its Characterization Related to Angiogenesis and Cancer

Masabumi Shibuya  1
Affiliations

Tyrosine Kinase Receptor Flt/VEGFR Family: Its Characterization Related to Angiogenesis and Cancer

Masabumi Shibuya. Genes Cancer. 2010 Nov.

Abstract

Ligands and their tyrosine kinase (TK) receptors regulate a variety of biological systems in animals. Vascular endothelial growth factor (VEGF) and its receptor (Flt/VEGFR family) system play a crucial role not only in physiological but also in most parts of pathological angiogenesis including cancer. Flt-1/VEGFR-1 and KDR/VEGFR-2 bind VEGF-A but have different functions on angiogenesis at early embryogenesis: Flt-1 has a negative role by trapping ligands, whereas KDR (Flk1 in mice) exerts a strong positive signal, resulting in a balance in blood vessel formation. At adult stages, however, both VEGFRs contribute to pathological angiogenesis either directly or through stimulation of migration/activation of macrophage lineage cells and stimulate tumor growth, metastasis, and inflammation. VEGFRs activate downstream signaling of the phospholipase Cγ-protein kinase C-MAP kinase pathway but not Ras pathway for cell proliferation. The VEGF-C/D and Flt-4/VEGFR-3 system regulates lymphangiogenesis. Thus, VEGFs as well as these receptor TKs are attractive targets for suppressing pathological angiogenesis.

Keywords: phospholipase C; tumor angiogenesis; tyrosine kinase receptor; vascular endothelial growth factor.

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Conflict of interest statement

The author declared no potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
The VEGF-VEGFR system in mammals. VEGF-A and 3 VEGFR genes are essential for normal angiogenesis during embryogenesis. Knockout mice of these genes are embryonic lethal due to abnormality of blood vessel formation. In the case of the VEGF-A gene, even the heterozygote mice die in embryogenesis because of the dysfunction of blood vessels.
Figure 2.
Figure 2.
Premetastatic activation in the lung via VEGFR-1 (Flt-1) signaling. Transplanted tumors in mice induce macrophage lineage cell migration and MMP9 expression in the lung before metastasis. VEGFR-1 signal–deficient mice (flt-1 TK–/– mice) show less migration of macrophages and MMP9 expression as well as decreased metastasis, indicating these processes to be partly dependent on VEGFR-1 TK signaling.
See this image and copyright information in PMC

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