| Title: |
TMPRSS2-ERG fusion promotes prostate cancer metastases in bone |
| Authors: |
Deplus, Rachel; Delliaux, Carine; Marchand, Nathalie; Flourens, Anne; Vanpouille, Nathalie; Leroy, Xavier; de Launoit, Yvan; Duterque-Coquillaud, Martine |
| Contributors: |
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 (M3T); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-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 CHU 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. |
| Source: |
ISSN: 1949-2553 ; Oncotarget ; https://hal.science/hal-02391621 ; Oncotarget, 2017, 8 (7), pp.11827-11840. ⟨10.18632/oncotarget.14399⟩. |
| Publisher Information: |
CCSD; Impact journals |
| Publication Year: |
2017 |
| Collection: |
LillOA (HAL Lille Open Archive, Université de Lille) |
| Subject Terms: |
prostate cancer; bone tropism; bone metastasis; TMPRSS2-ERG; MESH: Animals; MESH: Bone Neoplasms/genetics; MESH: Prostatic Neoplasms/pathology; MESH: Transfection; MESH: Bone Neoplasms/metabolism; MESH: Bone Neoplasms/secondary; MESH: Cell Line; Tumor; MESH: Cell Movement/physiology; MESH: Cell Proliferation/physiology; MESH: Heterografts; MESH: Humans; MESH: Male; MESH: Mice; SCID; MESH: Neoplasm Metastasis; MESH: Oncogene Proteins; Fusion/biosynthesis; Fusion/genetics; MESH: Prostatic Neoplasms/genetics; MESH: Prostatic Neoplasms/metabolism; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/28055969; PUBMED: 28055969; PUBMEDCENTRAL: PMC5355307 |
| DOI: |
10.18632/oncotarget.14399 |
| Availability: |
https://hal.science/hal-02391621; https://hal.science/hal-02391621v1/document; https://hal.science/hal-02391621v1/file/TMPRSS2-ERG_fusion_promotes_prostate.pdf; https://doi.org/10.18632/oncotarget.14399 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.A5080DB7 |
| Database: |
BASE |