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Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression.
Abrate, Alberto; Buono, Roberta; Canu, Tamara; Esposito, Antonio; Del Maschio, Alessandro; Lucianò, Roberta; Bettiga, Arianna; Colciago, Giorgia; Guazzoni, Giorgio; Benigni, Fabio; Hedlund, Petter; Altaner, Cestmir; Montorsi, Francesco; Cavarretta, Ilaria T R.
Afiliación
  • Abrate A; Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Buono R; Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Canu T; Department of Radiology, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Esposito A; Department of Radiology, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Del Maschio A; Department of Radiology, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Lucianò R; Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy; Department of Pathology, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Bettiga A; Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Colciago G; Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Guazzoni G; Department of Urology, IRCCS Ospedale San Raffaele, Turro, Milan, Italy.
  • Benigni F; Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Hedlund P; Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy; Department of Clinical Pharmacology, Linköping University, Sweden.
  • Altaner C; Cancer Research Institute, Slovak Academy of Sciences and St. Elisabeth Cancer Institute, Bratislava, Slovakia.
  • Montorsi F; Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Cavarretta IT; Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: cavarretta.ilaria@hsr.it.
Eur J Cancer ; 50(14): 2478-88, 2014 Sep.
Article en En | MEDLINE | ID: mdl-25060826
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Terapia Genética / Adenocarcinoma / Trasplante de Células Madre Mesenquimatosas / Células Madre Mesenquimatosas Tipo de estudio: Clinical_trials Límite: Animals / Humans / Male Idioma: En Revista: Eur J Cancer Año: 2014 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Terapia Genética / Adenocarcinoma / Trasplante de Células Madre Mesenquimatosas / Células Madre Mesenquimatosas Tipo de estudio: Clinical_trials Límite: Animals / Humans / Male Idioma: En Revista: Eur J Cancer Año: 2014 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido