Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours
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 t...
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| Formato: | Artículo publishedVersion |
| Lenguaje: | Inglés |
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2006
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00220795_v191_n1_p249_Onofri |
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paperaa:paper_00220795_v191_n1_p249_Onofri2023-06-12T16:43:41Z 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 Onofri, C. Theodoropoulou, M. Losa, M. Uhl, E. Lange, M. Arzt, E. Stalla, G.K. Renner, U. 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 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. 2006 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00220795_v191_n1_p249_Onofri |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
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 |
| spellingShingle |
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 Onofri, C. Theodoropoulou, M. Losa, M. Uhl, E. Lange, M. Arzt, E. Stalla, G.K. Renner, U. Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours |
| topic_facet |
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 |
| description |
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. |
| format |
Artículo Artículo publishedVersion |
| author |
Onofri, C. Theodoropoulou, M. Losa, M. Uhl, E. Lange, M. Arzt, E. Stalla, G.K. Renner, U. |
| author_facet |
Onofri, C. Theodoropoulou, M. Losa, M. Uhl, E. Lange, M. Arzt, E. Stalla, G.K. Renner, U. |
| author_sort |
Onofri, C. |
| title |
Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours |
| title_short |
Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours |
| title_full |
Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours |
| title_fullStr |
Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours |
| title_full_unstemmed |
Localization of vascular endothelial growth factor (VEGF) receptors in normal and adenomatous pituitaries: Detection of a non-endothelial function of VEGF in pituitary tumours |
| title_sort |
localization of vascular endothelial growth factor (vegf) receptors in normal and adenomatous pituitaries: detection of a non-endothelial function of vegf in pituitary tumours |
| publishDate |
2006 |
| url |
http://hdl.handle.net/20.500.12110/paper_00220795_v191_n1_p249_Onofri |
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