Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression

被引:40
作者
Abrate, Alberto [1 ]
Buono, Roberta [1 ]
Canu, Tamara [2 ]
Esposito, Antonio [2 ]
Del Maschio, Alessandro [2 ]
Luciano, Roberta [1 ,3 ]
Bettiga, Arianna [1 ]
Colciago, Giorgia [1 ]
Guazzoni, Giorgio [4 ]
Benigni, Fabio [1 ]
Hedlund, Petter [1 ,5 ]
Altaner, Cestmir [6 ,7 ]
Montorsi, Francesco [1 ]
Cavarretta, Ilaria T. R. [1 ]
机构
[1] IRCCS Osped San Raffaele, Urol Res Inst, Milan, Italy
[2] IRCCS Osped San Raffaele, Dept Radiol, Milan, Italy
[3] IRCCS Osped San Raffaele, Dept Pathol, Milan, Italy
[4] IRCCS Osped San Raffaele, Dept Urol, Milan, Italy
[5] Linkoping Univ, Dept Clin Pharmacol, S-58183 Linkoping, Sweden
[6] Slovak Acad Sci, Canc Res Inst, Bratislava, Slovakia
[7] St Elisabeth Canc Inst, Bratislava, Slovakia
关键词
Mesenchymal stem cells; Prodrug activating enzymes; Prostate cancer; TRAMP mice; Magnetic resonance imaging; ADIPOSE-TISSUE; BONE-MARROW; CYTOSINE DEAMINASE; MOUSE PROSTATE; STROMAL CELLS; CANCER; TRANSPLANTATION; LUNG; GLIOBLASTOMA; THERAPIES;
D O I
10.1016/j.ejca.2014.06.014
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2478 / 2488
页数:11
相关论文
共 41 条
[1]
Stem and progenitor cell-mediated tumor selective gene therapy [J].
Aboody, K. S. ;
Najbauer, J. ;
Danks, M. K. .
GENE THERAPY, 2008, 15 (10) :739-752
[2]
Stem cell based glioblastoma gene therapy [J].
Altaner, C. ;
Altanerova, V. .
NEOPLASMA, 2012, 59 (06) :756-760
[3]
Complete regression of glioblastoma by mesenchymal stem cells mediated prodrug gene therapy simulating clinical therapeutic scenario [J].
Altaner, Cestmir ;
Altanerova, Veronika ;
Cihova, Marina ;
Ondicova, Katarina ;
Rychly, Boris ;
Baciak, Ladislav ;
Mravec, Boris .
INTERNATIONAL JOURNAL OF CANCER, 2014, 134 (06) :1458-1465
[4]
Human adipose tissue-derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat glioblastoma [J].
Altanerova, Veronika ;
Cihova, Marina ;
Babic, Michal ;
Rychly, Boris ;
Ondicova, Katarina ;
Mravec, Boris ;
Altaner, Cestmir .
INTERNATIONAL JOURNAL OF CANCER, 2012, 130 (10) :2455-2463
[5]
Adipose Tissue-derived Mesenchymal Stem Cells Expressing Prodrug-converting Enzyme Inhibit Human Prostate Tumor Growth [J].
Cavarretta, Ilaria T. ;
Altanerova, Veronika ;
Matuskova, Miroslava ;
Kucerova, Lucia ;
Culig, Zoran ;
Altaner, Cestmir .
MOLECULAR THERAPY, 2010, 18 (01) :223-231
[6]
From bench to bedside for gene-directed enzyme prodrug therapy of cancer [J].
Dachs, GU ;
Tupper, J ;
Tozer, GM .
ANTI-CANCER DRUGS, 2005, 16 (04) :349-359
[7]
Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy [J].
Daldrup-Link, HE ;
Rudelius, M ;
Metz, S ;
Piontek, G ;
Pichler, B ;
Settles, M ;
Heinzmann, U ;
Schlegel, J ;
Oostendorp, RAJ ;
Rummeny, EJ .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2004, 31 (09) :1312-1321
[8]
Suspension Medium Influences Interaction of Mesenchymal Stromal Cells with Endothelium and Pulmonary Toxicity after Transplantation In Mice [J].
Deak, Erika ;
Ruester, Brigitte ;
Keller, Lisa ;
Eckert, Klaus ;
Fichtner, Iduna ;
Seifried, Erhard ;
Henschler, Reinhard .
CYTOTHERAPY, 2010, 12 (02) :260-264
[9]
Peripheral T cell tolerance occurs early during spontaneous prostate cancer development and can be rescued by dendritic cell immunization [J].
Degl'Innocenti, E ;
Grioni, M ;
Boni, A ;
Camporeale, A ;
Bertilaccio, MTS ;
Freschi, M ;
Monno, A ;
Arcelloni, C ;
Greenberg, NM ;
Bellone, M .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (01) :66-75
[10]
Migratory Properties of Mesenchymal Stem Cells [J].
Dittmar, Thomas ;
Entschladen, Frank .
MESENCHYMAL STEM CELLS: BASICS AND CLINICAL APPLICATION I, 2013, 129 :117-136