Human lactiferous mammary gland cells produce vascular endothelial growth factor (VEGF) and express the VEGF receptors, Flt-1 and KDR/Flk-1

Human milk contains a variety of growth factors. Recently, it was reported that vascular endothelial growth factor (VEGF) was one of them. We investigated milk VEGF isoforms, their functions, and VEGF receptors on mammary gland epithelial cells (MEC). The VEGF concentration in human milk was 74.3 +/- 34.9 ng/ml on the first day after delivery, and rapidly decreased in a couple of days to 6.2 +/- 2.3 ng/ml on the fifth day, and matured milk maintained about 4 ng/ml. In an MTT assay, human milk accelerated HUVEC proliferation and MV303, a neutralizing antibody of VEGF, blocked 17.3 % of the effect. Immunoprecipitation and Western blotting showed that VEGF121 and VEGF165 were contained in human colostrums, and RT-PCR of human MEC confirmed that VEGF121, VEGF165 and VEGF189 were present. By immunostaining of human breast tissues, RT-PCR of NIEC from human colostrum and measurement of the VEGF concentrations of conditioned media of cultured human NIEC, it was confirmed that VEGF was produced by NIEC. NIEC was also expressed VEGF receptors, flt-1 and Flk-1/KDR. These results speculate us that the existence of autocrine or paracrine system within breast tissue via VEGF receptors on NIEC and have a role in lactation. (C) 2002 Elsevier Science Ltd. All rights reserved.