title: TMPRSS2-ERG fusion promotes prostate cancer metastases in bone.
abstract: 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.
authors.affiliation: University Lille, CNRS, Institut Pasteur de Lille, UMR 8161 (M3T) Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Deplus
authors.affiliation: University Lille, CNRS, Institut Pasteur de Lille, UMR 8161 (M3T) Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Delliaux
authors.affiliation: University Lille, CNRS, Institut Pasteur de Lille, UMR 8161 (M3T) Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Marchand
authors.affiliation: University Lille, CNRS, Institut Pasteur de Lille, UMR 8161 (M3T) Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Flourens
authors.affiliation: University Lille, CNRS, Institut Pasteur de Lille, UMR 8161 (M3T) Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vanpouille
authors.affiliation: Institut de Pathologie Centre de Biologie Pathologie Centre Hospitalier Régional et Universitaire, F-59037 Lille, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leroy
authors.affiliation: University Lille, CNRS, Institut Pasteur de Lille, UMR 8161 (M3T) Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France.
authors.forename: Yvan
authors.initials: Y
authors.lastname: de Launoit
authors.affiliation: University Lille, CNRS, Institut Pasteur de Lille, UMR 8161 (M3T) Mechanisms of Tumorigenesis and Target Therapies, F-59000 Lille, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Duterque-Coquillaud
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014162:Transfection
chemical_list: D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human
keywords: TMPRSS2-ERG; bone metastasis; bone tropism; prostate cancer