HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression
Background: Prostate cancer (PCa) dissemination shows a tendency to develop in the bone, where heme oxygenase 1 (HO-1) plays a critical role in bone remodeling. Previously by LC/ESI-MSMS, we screened for HO-1 interacting proteins and identified annexin 2 (ANXA2). The aim of this study was to analyze...
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| Format: | Article |
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MDPI AG
2020-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/3/467 |
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| author | Nicolás Anselmino Juan Bizzotto Pablo Sanchis Sofia Lage-Vickers Emiliano Ortiz Pia Valacco Alejandra Paez Estefania Labanca Roberto Meiss Nora Navone Javier Cotignola Elba Vazquez Geraldine Gueron |
| author_facet | Nicolás Anselmino Juan Bizzotto Pablo Sanchis Sofia Lage-Vickers Emiliano Ortiz Pia Valacco Alejandra Paez Estefania Labanca Roberto Meiss Nora Navone Javier Cotignola Elba Vazquez Geraldine Gueron |
| author_sort | Nicolás Anselmino |
| collection | DOAJ |
| description | Background: Prostate cancer (PCa) dissemination shows a tendency to develop in the bone, where heme oxygenase 1 (HO-1) plays a critical role in bone remodeling. Previously by LC/ESI-MSMS, we screened for HO-1 interacting proteins and identified annexin 2 (ANXA2). The aim of this study was to analyze the relevance of ANXA2/HO-1 in PCa and bone metastasis. Methods: We assessed <i>ANXA2</i> levels using a co-culture transwell system of PC3 cells (pre-treated or not with hemin, an HO-1 specific inducer) and the pre-osteoclastic Raw264.7 cell line. Results: Under co-culture conditions, <i>ANXA2</i> mRNA levels were significantly modulated in both cell lines. Immunofluorescence analysis unveiled a clear ANXA2 reduction in cell membrane immunostaining for Raw264.7 under the same conditions. This effect was supported by the detection of a decrease in Ca<sup>2+</sup> concentration in the conditioned medium. HO-1 induction in tumor cells prevented both, the ANXA2 intracellular relocation and the decrease in Ca<sup>2+</sup> concentration. Further, secretome analysis revealed urokinase (uPA) as a key player in the communication between osteoclast progenitors and PC3 cells. To assess the clinical significance of ANXA2/HO-1, we performed a bioinformatics analysis and identified that low expression of each gene strongly associated with poor prognosis in PCa regardless of the clinico-pathological parameters assessed. Further, these genes appear to behave in a dependent manner. Conclusions: ANXA2/HO-1 rises as a critical axis in PCa. |
| first_indexed | 2024-12-14T03:47:42Z |
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| id | doaj.art-d823517b71734d97a786bf89f76fd299 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-14T03:47:42Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-d823517b71734d97a786bf89f76fd2992022-12-21T23:18:18ZengMDPI AGBiomolecules2218-273X2020-03-0110346710.3390/biom10030467biom10030467HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer ProgressionNicolás Anselmino0Juan Bizzotto1Pablo Sanchis2Sofia Lage-Vickers3Emiliano Ortiz4Pia Valacco5Alejandra Paez6Estefania Labanca7Roberto Meiss8Nora Navone9Javier Cotignola10Elba Vazquez11Geraldine Gueron12Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Inflamación y Cáncer, Buenos Aires C1428EGA, ArgentinaUniversidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Inflamación y Cáncer, Buenos Aires C1428EGA, ArgentinaUniversidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Inflamación y Cáncer, Buenos Aires C1428EGA, ArgentinaUniversidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Inflamación y Cáncer, Buenos Aires C1428EGA, ArgentinaUniversidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Inflamación y Cáncer, Buenos Aires C1428EGA, ArgentinaUniversidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Inflamación y Cáncer, Buenos Aires C1428EGA, ArgentinaUnidad de Transferencia Genética, Instituto de Oncología “Angel H Roffo”, Universidad de Buenos Aires, Buenos Aires C1417DTB, ArgentinaDepartment of Genitourinary Medical Oncology and the David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAAcademia Nacional de Medicina, Buenos Aires C1425ASU, ArgentinaDepartment of Genitourinary Medical Oncology and the David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAUniversidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Inflamación y Cáncer, Buenos Aires C1428EGA, ArgentinaUniversidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Inflamación y Cáncer, Buenos Aires C1428EGA, ArgentinaUniversidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Inflamación y Cáncer, Buenos Aires C1428EGA, ArgentinaBackground: Prostate cancer (PCa) dissemination shows a tendency to develop in the bone, where heme oxygenase 1 (HO-1) plays a critical role in bone remodeling. Previously by LC/ESI-MSMS, we screened for HO-1 interacting proteins and identified annexin 2 (ANXA2). The aim of this study was to analyze the relevance of ANXA2/HO-1 in PCa and bone metastasis. Methods: We assessed <i>ANXA2</i> levels using a co-culture transwell system of PC3 cells (pre-treated or not with hemin, an HO-1 specific inducer) and the pre-osteoclastic Raw264.7 cell line. Results: Under co-culture conditions, <i>ANXA2</i> mRNA levels were significantly modulated in both cell lines. Immunofluorescence analysis unveiled a clear ANXA2 reduction in cell membrane immunostaining for Raw264.7 under the same conditions. This effect was supported by the detection of a decrease in Ca<sup>2+</sup> concentration in the conditioned medium. HO-1 induction in tumor cells prevented both, the ANXA2 intracellular relocation and the decrease in Ca<sup>2+</sup> concentration. Further, secretome analysis revealed urokinase (uPA) as a key player in the communication between osteoclast progenitors and PC3 cells. To assess the clinical significance of ANXA2/HO-1, we performed a bioinformatics analysis and identified that low expression of each gene strongly associated with poor prognosis in PCa regardless of the clinico-pathological parameters assessed. Further, these genes appear to behave in a dependent manner. Conclusions: ANXA2/HO-1 rises as a critical axis in PCa.https://www.mdpi.com/2218-273X/10/3/467heme-oxygenase-1 (ho-1)prostate cancer (pca)annexin a2 (anxa2)bonemetastasisurokinase-plasminogen activator (upa) |
| spellingShingle | Nicolás Anselmino Juan Bizzotto Pablo Sanchis Sofia Lage-Vickers Emiliano Ortiz Pia Valacco Alejandra Paez Estefania Labanca Roberto Meiss Nora Navone Javier Cotignola Elba Vazquez Geraldine Gueron HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression Biomolecules heme-oxygenase-1 (ho-1) prostate cancer (pca) annexin a2 (anxa2) bone metastasis urokinase-plasminogen activator (upa) |
| title | HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression |
| title_full | HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression |
| title_fullStr | HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression |
| title_full_unstemmed | HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression |
| title_short | HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression |
| title_sort | ho 1 interactors involved in the colonization of the bone niche role of anxa2 in prostate cancer progression |
| topic | heme-oxygenase-1 (ho-1) prostate cancer (pca) annexin a2 (anxa2) bone metastasis urokinase-plasminogen activator (upa) |
| url | https://www.mdpi.com/2218-273X/10/3/467 |
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