Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer
Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Once a tumor is established it may attain further characteristics via mutations or hypoxia, which stimulate new blood vessels. Angiogenesis is a hallmark in the pathogenesis of cancer and inflammatory diseases that...
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2011
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09696970_v14_n4_p467_Ferrando http://hdl.handle.net/20.500.12110/paper_09696970_v14_n4_p467_Ferrando |
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paper:paper_09696970_v14_n4_p467_Ferrando2023-06-08T15:59:04Z Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer Angiogenesis Heme oxygenase 1 (HO-1) NF-κB Prostate cancer VEGF CD34 antigen gelatinase B heme oxygenase 1 hypoxia inducible factor 1alpha immunoglobulin enhancer binding protein reactive oxygen metabolite vasculotropin A vasculotropin C vasculotropin receptor 2 very late activation antigen 5 animal experiment animal model animal tissue article controlled study gene expression regulation gene overexpression genetic transfection heme oxygenase 1 gene in vivo study male microvasculature mouse nonhuman oxidative stress priority journal prostate cancer receptor down regulation signal transduction transcription regulation tumor gene tumor vascularization Analysis of Variance Animals DNA Primers Gene Expression Regulation, Neoplastic Heme Oxygenase-1 Histological Techniques Humans Immunohistochemistry Luciferases Male Mice Mice, Nude Neovascularization, Pathologic Plasmids Prostatic Neoplasms Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor C Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Once a tumor is established it may attain further characteristics via mutations or hypoxia, which stimulate new blood vessels. Angiogenesis is a hallmark in the pathogenesis of cancer and inflammatory diseases that may predispose to cancer. Heme oxygenase-1 (HO-1) counteracts oxidative and inflammatory damage and was previously reported to play a key role in prostate carcinogenesis. To gain insight into the anti-tumoral properties of HO-1, we investigated its capability to modulate PCa associated-angiogenesis. In the present study, we identified in PC3 cells a set of inflammatory and pro-angiogenic genes down-regulated in response to HO-1 overexpression, in particular VEGFA, VEGFC, HIF1α and α5β1 integrin. Our results indicated that HO-1 counteracts oxidative imbalance reducing ROS levels. An in vivo angiogenic assay showed that intradermal inoculation of PC3 cells stable transfected with HO-1 (PC3HO-1) generated tumours less vascularised than controls, with decreased microvessel density and reduced CD34 and MMP9 positive staining. Interestingly, longer term grown PC3HO-1 xenografts displayed reduced neovascularization with the subsequent down-regulation of VEGFR2 expression. Additionally, HO-1 repressed nuclear factor κB (NF-κB)-mediated transcription from an NF-κB responsive luciferase reporter construct, which strongly suggests that HO-1 may regulate angiogenesis through this pathway. Taken together, these data supports a key role of HO-1 as a modulator of the angiogenic switch in prostate carcinogenesis ascertaining it as a logical target for intervention therapy. © 2011 Springer Science+Business Media B.V. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09696970_v14_n4_p467_Ferrando http://hdl.handle.net/20.500.12110/paper_09696970_v14_n4_p467_Ferrando |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Angiogenesis Heme oxygenase 1 (HO-1) NF-κB Prostate cancer VEGF CD34 antigen gelatinase B heme oxygenase 1 hypoxia inducible factor 1alpha immunoglobulin enhancer binding protein reactive oxygen metabolite vasculotropin A vasculotropin C vasculotropin receptor 2 very late activation antigen 5 animal experiment animal model animal tissue article controlled study gene expression regulation gene overexpression genetic transfection heme oxygenase 1 gene in vivo study male microvasculature mouse nonhuman oxidative stress priority journal prostate cancer receptor down regulation signal transduction transcription regulation tumor gene tumor vascularization Analysis of Variance Animals DNA Primers Gene Expression Regulation, Neoplastic Heme Oxygenase-1 Histological Techniques Humans Immunohistochemistry Luciferases Male Mice Mice, Nude Neovascularization, Pathologic Plasmids Prostatic Neoplasms Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor C |
| spellingShingle |
Angiogenesis Heme oxygenase 1 (HO-1) NF-κB Prostate cancer VEGF CD34 antigen gelatinase B heme oxygenase 1 hypoxia inducible factor 1alpha immunoglobulin enhancer binding protein reactive oxygen metabolite vasculotropin A vasculotropin C vasculotropin receptor 2 very late activation antigen 5 animal experiment animal model animal tissue article controlled study gene expression regulation gene overexpression genetic transfection heme oxygenase 1 gene in vivo study male microvasculature mouse nonhuman oxidative stress priority journal prostate cancer receptor down regulation signal transduction transcription regulation tumor gene tumor vascularization Analysis of Variance Animals DNA Primers Gene Expression Regulation, Neoplastic Heme Oxygenase-1 Histological Techniques Humans Immunohistochemistry Luciferases Male Mice Mice, Nude Neovascularization, Pathologic Plasmids Prostatic Neoplasms Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor C Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer |
| topic_facet |
Angiogenesis Heme oxygenase 1 (HO-1) NF-κB Prostate cancer VEGF CD34 antigen gelatinase B heme oxygenase 1 hypoxia inducible factor 1alpha immunoglobulin enhancer binding protein reactive oxygen metabolite vasculotropin A vasculotropin C vasculotropin receptor 2 very late activation antigen 5 animal experiment animal model animal tissue article controlled study gene expression regulation gene overexpression genetic transfection heme oxygenase 1 gene in vivo study male microvasculature mouse nonhuman oxidative stress priority journal prostate cancer receptor down regulation signal transduction transcription regulation tumor gene tumor vascularization Analysis of Variance Animals DNA Primers Gene Expression Regulation, Neoplastic Heme Oxygenase-1 Histological Techniques Humans Immunohistochemistry Luciferases Male Mice Mice, Nude Neovascularization, Pathologic Plasmids Prostatic Neoplasms Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor C |
| description |
Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Once a tumor is established it may attain further characteristics via mutations or hypoxia, which stimulate new blood vessels. Angiogenesis is a hallmark in the pathogenesis of cancer and inflammatory diseases that may predispose to cancer. Heme oxygenase-1 (HO-1) counteracts oxidative and inflammatory damage and was previously reported to play a key role in prostate carcinogenesis. To gain insight into the anti-tumoral properties of HO-1, we investigated its capability to modulate PCa associated-angiogenesis. In the present study, we identified in PC3 cells a set of inflammatory and pro-angiogenic genes down-regulated in response to HO-1 overexpression, in particular VEGFA, VEGFC, HIF1α and α5β1 integrin. Our results indicated that HO-1 counteracts oxidative imbalance reducing ROS levels. An in vivo angiogenic assay showed that intradermal inoculation of PC3 cells stable transfected with HO-1 (PC3HO-1) generated tumours less vascularised than controls, with decreased microvessel density and reduced CD34 and MMP9 positive staining. Interestingly, longer term grown PC3HO-1 xenografts displayed reduced neovascularization with the subsequent down-regulation of VEGFR2 expression. Additionally, HO-1 repressed nuclear factor κB (NF-κB)-mediated transcription from an NF-κB responsive luciferase reporter construct, which strongly suggests that HO-1 may regulate angiogenesis through this pathway. Taken together, these data supports a key role of HO-1 as a modulator of the angiogenic switch in prostate carcinogenesis ascertaining it as a logical target for intervention therapy. © 2011 Springer Science+Business Media B.V. |
| title |
Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer |
| title_short |
Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer |
| title_full |
Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer |
| title_fullStr |
Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer |
| title_full_unstemmed |
Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer |
| title_sort |
heme oxygenase 1 (ho-1) challenges the angiogenic switch in prostate cancer |
| publishDate |
2011 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09696970_v14_n4_p467_Ferrando http://hdl.handle.net/20.500.12110/paper_09696970_v14_n4_p467_Ferrando |
| _version_ |
1768543713332559872 |