Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours

• Autores: Onofri, C.; Theodoropoulou, M.; Losa, M.; Uhl, E.; Lange, M.; Arzt, E.; Stalla, G.K.; Renner, U.
• Año de publicación: 2006
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: J. Endocrinol. 2006;191(1):249-261
• Materia: cyclin D1; messenger RNA; neuropilin 1; phosphatidylinositol 3 kinase; placental growth factor; protein bcl 2; vasculotropin A; vasculotropin receptor; vasculotropin receptor 1; vasculotropin receptor 2; adult; aged; animal cell; article; cell proliferation; controlled study; endocrine cell; endothelium cell; epithelium tumor; female; gene expression; human; human cell; human tissue; hypophysis adenoma; immunohistochemistry; in situ hybridization; male; nonhuman; nucleotide sequence; priority journal; protein expression; protein function; protein localization; rat; real time polymerase chain reaction; tumor growth; tumor vascularization; 1-Phosphatidylinositol 3-Kinase; Adenoma; Adult; Aged; Animals; Antibodies, Monoclonal; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Chromones; Endothelial Cells; Female; Humans; Immunohistochemistry; In Situ Hybridization; Ligands; Male; Middle Aged; Morpholines; Neuropilin-1; Pituitary Gland; Pituitary Neoplasms; Rats; Receptors, Vascular Endothelial Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; Somatotrophs; Stimulation, Chemical; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

As for any solid tumour, pituitary adenoma expansion is dependent on neovascularization through angiogenesis. In this process, vascular endothelial growth factor (VEGF) and its receptors VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) may play an outstanding role. The intention of this work was to study the expression/localization and possible function of VEGF receptors in pituitary adenomas. VEGF receptor mRNA and protein expression was studied by in situ hybridization, immunohistochemistry and RT-PCR in 6 normal human pituitaries, 39 human pituitary adenomas and 4 rodent pituitary adenoma cell lines. VEGFR-1 expressing somatotroph MtT-S cells were used as a model to study the role of VEGF on cell proliferation and to elucidate the underlying mechanism of action. In normal pituitaries, VEGFR-1 was detected in endocrine cells, whereas VEGFR-2 and NRP-1 were exclusively expressed in endothelial cells. In pituitary tumours, a heterogeneous VEGFR expression pattern was observed by IHC. VEGFR-1, VEGFR-2 and NRP-1 were detected in 24, 18 and 17 adenomas respectively. In the adenomas, VEGFR-1 was expressed in epithelial tumour cells and VEGFR-2/NRP-1 in vessel endothelial cells. Functional studies in VEGFR-1-positive MtT-S cells showed that the ligands of VIEGFR-1 significantly stimulated cell proliferation. This effect was mediated through the phosphatidylinositol-3-kinase-signalling pathway and involves induction of cyclin D1 and Bcl-2. Based on our results, we speculate that the ligands of VEGF receptors, such as VEGF-A and placenta growth factor, not only play a role in angiogenesis in pituitary adenomas, but also affect the growth of pituitary tumour cells through VEGFR-1. © 2006 Society for Endocrinology.