TMPRSS2-ERG fusion promotes prostate cancer metastases in bone
| Autor: | Anne Flourens, Carine Delliaux, Yvan de Launoit, Xavier Leroy, Rachel Deplus, Martine Duterque-Coquillaud, Nathalie Marchand, Nathalie Vanpouille |
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| Přispěvatelé: | Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 (M3T), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This work was supported by grants from the Centre national de la recherche scientifique (CNRS), La Ligue contre le Cancer (Comité du Pas-de-Calais) and the Institut national du cancer (INCa_4419). CD is a recipient of Ph.D. fellowships from the Institut Pasteur of Lille/Nord-Pas-de-Calais Regional Council (Région Nord-Pas-de Calais) and the FRM (Fondation pour la Recheche Médicale)., We thank Tian V. Tian, Edith Bonnelye and Olivier Morales for help and advices in mouse experiments. We thank the Microscopy-Imaging-Cytometry Facility of the BioImaging Center Lille Nord-de-France for access to instruments and technical advice. We thank also Francois Fuks for his helpful advices in manuscript redaction., de Launoit, Yvan |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pathology Oncogene Proteins Fusion TMPRSS2-ERG MESH: Cell Movement/physiology [SDV]Life Sciences [q-bio] Mice SCID urologic and male genital diseases Metastasis Transcriptome Cell Proliferation -- physiology Prostate cancer Cell Movement -- physiology Mice 0302 clinical medicine Cell Movement MESH: Animals MESH: Oncogene Proteins Fusion/genetics Neoplasm Metastasis MESH: Mice SCID bone metastasis Prostatic Neoplasms -- genetics -- metabolism -- pathology Bone metastasis Cell migration Sciences bio-médicales et agricoles MESH: Prostatic Neoplasms/pathology prostate cancer bone tropism [SDV] Life Sciences [q-bio] Oncogene Proteins Fusion -- biosynthesis -- genetics Oncology 030220 oncology & carcinogenesis MESH: Bone Neoplasms/metabolism Heterografts MESH: Bone Neoplasms/secondary MESH: Bone Neoplasms/genetics Research Paper medicine.medical_specialty MESH: Cell Line Tumor Bone Neoplasms Transfection TMPRSS2 03 medical and health sciences Cell Line Tumor medicine Animals Humans MESH: Mice Tropism Cell Proliferation MESH: Prostatic Neoplasms/genetics Bone Neoplasms -- genetics -- metabolism -- secondary MESH: Humans MESH: Oncogene Proteins Fusion/biosynthesis business.industry MESH: Transfection MESH: Prostatic Neoplasms/metabolism Prostatic Neoplasms MESH: Cell Proliferation/physiology medicine.disease MESH: Neoplasm Metastasis MESH: Male 030104 developmental biology Cancer cell MESH: Heterografts business |
| Zdroj: | Oncotarget Oncotarget, Impact journals, 2017, 8 (7), pp.11827-11840. ⟨10.18632/oncotarget.14399⟩ Oncotarget, 2017, 8 (7), pp.11827-11840. ⟨10.18632/oncotarget.14399⟩ Oncotarget, 8 (7 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.14399⟩ |
| Popis: | Bone metastasis is the major deleterious event in prostate cancer (PCa). TMPRSS2-ERG fusion is one of the most common chromosomic rearrangements in PCa. However, its implication in bone metastasis development is still unclear. Since bone metastasis starts with the tropism of cancer cells to bone through specific migratory and invasive processes involving osteomimetic capabilities, it is crucial to better our understanding of the influence of TMPRSS2-ERG expression in the mechanisms underlying the bone tropism properties of PCa cells. We developed bioluminescent cell lines expressing the TMPRSS2-ERG fusion in order to assess its role in tumor growth and bone metastasis appearance in a mouse model. First, we showed that the TMPRSS2-ERG fusion increases cell migration and subcutaneous tumor size. Second, using intracardiac injection experiments in mice, we showed that the expression of TMPRSS2-ERG fusion increases the number of metastases in bone. Moreover, TMPRSS2-ERG affects the pattern of metastatic spread by increasing the incidence of tumors in hind limbs and spine, which are two of the most frequent sites of human PCa metastases. Finally, transcriptome analysis highlighted a series of genes regulated by the fusion and involved in the metastatic process. Altogether, our work indicates that TMPRSS2-ERG increases bone tropism of PCa cells and metastasis development. info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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