Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression

Alberto Abrate, Roberta Buono, Tamara Canu, Antonio Esposito, Alessandro Del Maschio, Roberta Lucianò, Arianna Bettiga, Giorgia Colciago, Giorgio Guazzoni, Fabio Benigni, Petter Hedlund, Cestmir Altaner, Francesco Montorsi, Ilaria T R Cavarretta

Research output: Contribution to journalArticlepeer-review

Abstract

Mesenchymal stem cells (MSC) as vehicles of therapeutic genes represent a unique tool to activate drugs within a neoplastic mass due to their property to home and engraft into tumours. In particular, MSC expressing the cytosine deaminase::uracil phosphoribosyltransferase (CD-MSC) have been previously demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks to their ability to convert the non-toxic 5-fluorocytosine into the antineoplastic 5-fluorouracil. Since both the immune system and the tumour microenvironment play a crucial role in directing cancer progression, in order to advance towards clinical applications, we tested the therapeutic potential of this approach on animal models that develop autochthonous prostate cancer and preserve an intact immune system. As cell vectors, we employed adipose-tissue and bone-marrow MSC. CD-MSC toxicity on murine prostate cancer cells and tumour tropism were verified in vitro and ex-vivo before starting the preclinical studies. Magnetic Resonance Imaging was utilised to follow orthotopic tumour progression. We demonstrated that intravenous injections of CD-MSC cells, followed by intraperitoneal administration of 5-fluorocytosine, caused tumour regression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which develops aggressive and spontaneous prostate cancer. These results add new insights to the therapeutic potential of specifically engineered MSC in prostate cancer disease.

Original languageEnglish
JournalEuropean Journal of Cancer
DOIs
Publication statusAccepted/In press - 2014

Keywords

  • Magnetic resonance imaging
  • Mesenchymal stem cells
  • Prodrug activating enzymes
  • Prostate cancer
  • TRAMP mice

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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