Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer

Ruggero De Maria Marchiano, Valeria Coppola, Federica Francescangeli, M. Musumeci, V. Coppola, A. Addario, M. Patrizii, M. Maugeri-Saccá, L. Memeo, C. Colarossi, F. Francescangeli, M. Biffoni, D. Collura, A. Giacobbe, L. D'Urso, M. Falchi, M. A. Venneri, G. Muto, D. Bonci

Risultato della ricerca: Contributo in rivistaArticolo in rivista

188 Citazioni (Scopus)

Abstract

The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer. © 2011 Macmillan Publishers Limited All rights reserved.
Lingua originaleEnglish
pagine (da-a)4231-4242
Numero di pagine12
RivistaOncogene
Volume30
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Aged
  • Aged, 80 and over
  • Animals
  • Blotting, Western
  • Cancer Research
  • Cell Line, Tumor
  • Down-Regulation
  • Fibroblast Growth Factor 2
  • Fibroblasts
  • Gene Expression Regulation, Neoplastic
  • Genetics
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs
  • Middle Aged
  • Molecular Biology
  • Neoplasms, Experimental
  • Phosphorylation
  • Prostatic Neoplasms
  • Proto-Oncogene Proteins c-akt
  • Receptor, Fibroblast Growth Factor, Type 1
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Heterologous
  • Tumor Microenvironment
  • cancer progression
  • miRNA
  • microenvironment

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