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Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality.
Tse, B W C; Volpert, M; Ratther, E; Stylianou, N; Nouri, M; McGowan, K; Lehman, M L; McPherson, S J; Roshan-Moniri, M; Butler, M S; Caradec, J; Gregory-Evans, C Y; McGovern, J; Das, R; Takhar, M; Erho, N; Alshalafa, M; Davicioni, E; Schaeffer, E M; Jenkins, R B; Ross, A E; Karnes, R J; Den, R B; Fazli, L; Gregory, P A; Gleave, M E; Williams, E D; Rennie, P S; Buttyan, R; Gunter, J H; Selth, L A; Russell, P J; Nelson, C C; Hollier, B G.
Afiliação
  • Tse BWC; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Volpert M; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Ratther E; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Stylianou N; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Nouri M; Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
  • McGowan K; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Lehman ML; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • McPherson SJ; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Roshan-Moniri M; Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
  • Butler MS; Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
  • Caradec J; Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
  • Gregory-Evans CY; Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
  • McGovern J; Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
  • Das R; Dame Roma Mitchell Cancer Research Laboratories and Freemason's Foundation Centre for Men's Health, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
  • Takhar M; GenomeDX Biosciences, Vancouver, British Columbia, Canada.
  • Erho N; GenomeDX Biosciences, Vancouver, British Columbia, Canada.
  • Alshalafa M; GenomeDX Biosciences, Vancouver, British Columbia, Canada.
  • Davicioni E; GenomeDX Biosciences, Vancouver, British Columbia, Canada.
  • Schaeffer EM; Department of Urology, Northwestern University, Chicago, IL, USA.
  • Jenkins RB; Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
  • Ross AE; Department of Urology, Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
  • Karnes RJ; Department of Urology, Mayo Clinic, Rochester, MN, USA.
  • Den RB; Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
  • Fazli L; Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
  • Gregory PA; Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, South Australia, Australia.
  • Gleave ME; Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
  • Williams ED; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Rennie PS; Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
  • Buttyan R; Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
  • Gunter JH; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Selth LA; Dame Roma Mitchell Cancer Research Laboratories and Freemason's Foundation Centre for Men's Health, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
  • Russell PJ; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Nelson CC; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
  • Hollier BG; Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Brisbane, Queensland, Australia.
Oncogene ; 36(24): 3417-3427, 2017 06 15.
Article em En | MEDLINE | ID: mdl-28092670
Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define NRP1 as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC). Using short hairpin RNA (shRNA)-mediated suppression of NRP1, we demonstrate that NRP1 regulates the mesenchymal phenotype of mCRPC cell models and the invasive and metastatic dissemination of tumor cells in vivo. In patients, immunohistochemical staining of tissue microarrays and mRNA expression analyses revealed a positive association between NRP1 expression and increasing Gleason grade, pathological T score, positive lymph node status and primary therapy failure. Furthermore, multivariate analysis of several large clinical prostate cancer (PCa) cohorts identified NRP1 expression at radical prostatectomy as an independent prognostic biomarker of biochemical recurrence after radiation therapy, metastasis and cancer-specific mortality. This study identifies NRP1 for the first time as a novel androgen-suppressed gene upregulated during the adaptive response of prostate tumors to ATTs and a prognostic biomarker of clinical metastasis and lethal PCa.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Regulação para Cima / Neuropilina-1 / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Guideline / Prognostic_studies Limite: Humans / Male Idioma: En Revista: Oncogene Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Austrália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Regulação para Cima / Neuropilina-1 / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Guideline / Prognostic_studies Limite: Humans / Male Idioma: En Revista: Oncogene Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Austrália