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Ferrando, M.; Gueron, G.; Elguero, B.; Giudice, J.; Salles, A.; Leskow, F.C.; Jares-Erijman, E.A.; Colombo, L.; Meiss, R.; Navone, N.; De Siervi, A.; Vazquez, E. "Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer" (2011) Angiogenesis. 14(4):467-479
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Abstract:

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.

Registro:

Documento: Artículo
Título:Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer
Autor:Ferrando, M.; Gueron, G.; Elguero, B.; Giudice, J.; Salles, A.; Leskow, F.C.; Jares-Erijman, E.A.; Colombo, L.; Meiss, R.; Navone, N.; De Siervi, A.; Vazquez, E.
Filiación:Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 2do Piso, Buenos Aires 1428, Argentina
Department of Organic Chemistry, School of Sciences, Ciudad Universitaria, 2do Piso, Buenos Aires 1428, Argentina
Research Area, Inst of Oncology A.H.Roffo, University of Buenos Aires, Buenos Aires, Argentina
Department of Pathology, Institute of Oncological Studies, National Academy of Medicine, Pacheco de Melo 3081, Buenos Aires 1425, Argentina
Department of Genitourinary Medical Oncology, University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, United States
Palabras clave: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
Año:2011
Volumen:14
Número:4
Página de inicio:467
Página de fin:479
DOI: http://dx.doi.org/10.1007/s10456-011-9230-4
Título revista:Angiogenesis
Título revista abreviado:Angiogenesis
ISSN:09696970
CODEN:AGIOF
CAS:gelatinase B, 146480-36-6; vasculotropin A, 489395-96-2; vasculotropin C, 171342-42-0, 185969-81-7; DNA Primers; HMOX1 protein, human, 1.14.99.3; Heme Oxygenase-1, 1.14.99.3; Luciferases, 1.13.12.-; Reactive Oxygen Species; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor C
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09696970_v14_n4_p467_Ferrando

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Citas:

---------- APA ----------
Ferrando, M., Gueron, G., Elguero, B., Giudice, J., Salles, A., Leskow, F.C., Jares-Erijman, E.A.,..., Vazquez, E. (2011) . Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer. Angiogenesis, 14(4), 467-479.
http://dx.doi.org/10.1007/s10456-011-9230-4
---------- CHICAGO ----------
Ferrando, M., Gueron, G., Elguero, B., Giudice, J., Salles, A., Leskow, F.C., et al. "Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer" . Angiogenesis 14, no. 4 (2011) : 467-479.
http://dx.doi.org/10.1007/s10456-011-9230-4
---------- MLA ----------
Ferrando, M., Gueron, G., Elguero, B., Giudice, J., Salles, A., Leskow, F.C., et al. "Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer" . Angiogenesis, vol. 14, no. 4, 2011, pp. 467-479.
http://dx.doi.org/10.1007/s10456-011-9230-4
---------- VANCOUVER ----------
Ferrando, M., Gueron, G., Elguero, B., Giudice, J., Salles, A., Leskow, F.C., et al. Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer. Angiogenesis. 2011;14(4):467-479.
http://dx.doi.org/10.1007/s10456-011-9230-4