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Abstract:

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.

Registro:

Documento: Artículo
Título:Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours
Autor:Onofri, C.; Theodoropoulou, M.; Losa, M.; Uhl, E.; Lange, M.; Arzt, E.; Stalla, G.K.; Renner, U.
Filiación:Istituto San Raffaele, Neurological Department, Milano, Italy
Ludwig-Maximillians University, Neurosurgical Department, Munich, Germany
Klinikum Villingen-Schwenningen, Neurosurgical Department, Villingen-Schwenningen, Germany
Laboratorio de Fisología y Biología Molecular, Departamento Ciencias Biológicas, FCEN-Universidad de Buenos Aires, Buenos Aires, Argentina
Max-Planck-Institute of Psychiatry, Neuroendocrinology Group, Kraepelinstr. 10, D-80804 Munich, Germany
Palabras clave: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
Año:2006
Volumen:191
Número:1
Página de inicio:249
Página de fin:261
DOI: http://dx.doi.org/10.1677/joe.1.06992
Título revista:Journal of Endocrinology
Título revista abreviado:J. Endocrinol.
ISSN:00220795
CODEN:JOENA
CAS:neuropilin 1, 214210-47-6, 339035-30-2; phosphatidylinositol 3 kinase, 115926-52-8; protein bcl 2, 219306-68-0; vasculotropin A, 489395-96-2; vasculotropin receptor, 301253-48-5; 1-Phosphatidylinositol 3-Kinase, EC 2.7.1.137; 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, 154447-36-6; Antibodies, Monoclonal; Chromones; Ligands; Morpholines; Neuropilin-1, 144713-63-3; Receptors, Vascular Endothelial Growth Factor, EC 2.7.1.112; Vascular Endothelial Growth Factor A; vascular endothelial growth factor A, human; Vascular Endothelial Growth Factor Receptor-1, EC 2.7.1.112; Vascular Endothelial Growth Factor Receptor-2, EC 2.7.1.112
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00220795_v191_n1_p249_Onofri.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00220795_v191_n1_p249_Onofri

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Citas:

---------- APA ----------
Onofri, C., Theodoropoulou, M., Losa, M., Uhl, E., Lange, M., Arzt, E., Stalla, G.K.,..., Renner, U. (2006) . Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours. Journal of Endocrinology, 191(1), 249-261.
http://dx.doi.org/10.1677/joe.1.06992
---------- CHICAGO ----------
Onofri, C., Theodoropoulou, M., Losa, M., Uhl, E., Lange, M., Arzt, E., et al. "Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours" . Journal of Endocrinology 191, no. 1 (2006) : 249-261.
http://dx.doi.org/10.1677/joe.1.06992
---------- MLA ----------
Onofri, C., Theodoropoulou, M., Losa, M., Uhl, E., Lange, M., Arzt, E., et al. "Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours" . Journal of Endocrinology, vol. 191, no. 1, 2006, pp. 249-261.
http://dx.doi.org/10.1677/joe.1.06992
---------- VANCOUVER ----------
Onofri, C., Theodoropoulou, M., Losa, M., Uhl, E., Lange, M., Arzt, E., et al. Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours. J. Endocrinol. 2006;191(1):249-261.
http://dx.doi.org/10.1677/joe.1.06992