Involvement of Flt-1 (VEGF receptor-1) in cancer and preeclampsia

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.