Nerve growth factor–endothelial cell interaction leads to angiogenesis in vitro and in vivo
- 21 June 2002
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 16 (10), 1307-1309
- https://doi.org/10.1096/fj.01-1000fje
Abstract
Nerve growth factor (NGF) has important functions during embryonic development and on various tissues and organs under normal and pathological conditions during the extrauterine life. RT-PCR analysis and immunological methods demonstrate that human umbilical vein endothelial cells (HUVECs) express the NGF receptors trkA(NGFR) and p75NTR. NGF treatment caused a rapid phosphorylation of trkA(NGFR) in HUVECs, determining a parallel increase of phosphorylated ERK1/2. Accordingly, NGF induced a significant increase in HUVEC proliferation that was abolished by the trkA(NGFR) inhibitor K252a. Also, HUVECs express significant levels of NGF under standard culture conditions that were up-regulated during serum starvation. Endogenous NGF was responsible for the basal levels of trkA(NGFR) and ERK1/2 phosphorylation observed in untreated HUVEC cultures. Finally, NGF exerted a potent, direct, angiogenic activity in vivo when delivered onto the chorioallantoic membrane of the chicken embryo. The data indicate that NGF may play an important role in blood vessel formation in the nervous system and in several pathological processes, including tumors and inflammatory diseases. Unraveling mechanisms of NGF-dependent angiogenesis could provide valuable tools for novel therapeutic approaches in antiangiogenic therapy.Keywords
Funding Information
- Associazione Italiana per la Lotta al Neuroblastoma
- Center for Neuroscience Research
- Associazione Italiana per la Ricerca sul Cancro
- Istituto Superiore di Sanità
This publication has 28 references indexed in Scilit:
- Neurotrophin receptor structure and interactionsPharmaceutica Acta Helvetiae, 2000
- Mitogenic Effect of Nerve Growth Factor (NGF) in LNCaP Prostate Adenocarcinoma Cells: Role of the High- and Low-Affinity NGF ReceptorsMolecular Endocrinology, 2000
- Nerve growth factor: a neurotrophin with activity on cells of the immune systemMicroscopy Research and Technique, 1999
- p75NTR: A study in contrastsCell Death & Differentiation, 1998
- Role of neurotrophins and their receptors in human neuroblastomas: a primary culture studyEuropean Journal Of Cancer, 1997
- Expression of human p140trk receptors in p140trk-deficient, PC12/endothelial cells results in nerve growth factor-induced signal transduction and DNA synthesisJournal of Cellular Biochemistry, 1997
- Nerve growth factor effects on human and mouse melanoma cell invasion and heparanase productionInternational Journal of Cancer, 1993
- Distribution of Nerve Growth Factor-Like Protein and Nerve Growth Factor Receptor in Human Benign Prostatic Hyperplasia and Prostatic AdenocarcinomaJournal of Urology, 1992
- The changing scene of neurotrophic factorsTrends in Neurosciences, 1991
- The Nerve Growth Factor 35 Years LaterScience, 1987