title: Involvement of Flt-1 (VEGF receptor-1) in cancer and preeclampsia.
abstract: We previously isolated a novel tyrosine kinase receptor, Flt-1, now known as VEGF-receptor (VEGFR)-1. The VEGF-VEGFR system plays a pivotal role in not only physiological but also pathological angiogenesis. We examined the role of Flt-1 in carcinogenesis using Flt-1-signal-deficient (Flt-1 TK-/-) mice, and found that this receptor stimulates tumor growth and metastasis most likely via macrophages, making it an important potential target in the treatment of cancer. In addition to the full-length receptor, the Flt-1 gene produces a soluble protein, sFlt-1, an endogenous VEGF-inhibitor. sFlt-1 is expressed in trophoblasts of the placenta between fetal and maternal blood vessels, suggesting it to be a barrier against extreme VEGF-signaling. Abnormally high expression of sFlt-1 occurs in most preeclampsia patients, whose main symptoms are hypertension and proteinurea. In cancer patients, strong suppression of VEGF-VEGFR by drugs induces similar side effects including hypertension. These results indicate a close relationship between abnormal VEGF-block and hypertension/proteinurea. sFlt-1 is an attractive target for the control of preeclampsia.
authors.affiliation: Jobu University, Gunma, Japan. shibuya@ims.u-tokyo.ac.jp
authors.forename: Masabumi
authors.initials: M
authors.lastname: Shibuya
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy; D018919:Neovascularization, Physiologic; D010802:Phylogeny; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000235:genetics
chemical_list: D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1