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Toro L, Bohovic R, Matuskova M, et al. Metastatic Ovarian Cancer Can Be Efficiently Treated by Genetically Modified Mesenchymal Stromal Cells. Stem Cells Dev. 2016;25(21):1640-1651doi: 10.1089/scd.2016.0064.
Toro, L., Bohovic, R., Matuskova, M., Smolkova, B., & Kucerova, L. (2016). Metastatic Ovarian Cancer Can Be Efficiently Treated by Genetically Modified Mesenchymal Stromal Cells. Stem cells and development, 25(21), 1640-1651. https://doi.org/10.1089/scd.2016.0064
Toro, Lenka, et al. "Metastatic Ovarian Cancer Can Be Efficiently Treated by Genetically Modified Mesenchymal Stromal Cells." Stem cells and development vol. 25,21 (2016): 1640-1651. doi: https://doi.org/10.1089/scd.2016.0064
Toro L, Bohovic R, Matuskova M, Smolkova B, Kucerova L. Metastatic Ovarian Cancer Can Be Efficiently Treated by Genetically Modified Mesenchymal Stromal Cells. Stem Cells Dev. 2016 Nov 01;25(21):1640-1651. doi: 10.1089/scd.2016.0064. Epub 2016 Aug 16. PMID: 27539058.
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Stem Cells Dev. 2016 Nov 01;25(21):1640-1651. doi: 10.1089/scd.2016.0064. Epub 2016 Aug 16.

Metastatic Ovarian Cancer Can Be Efficiently Treated by Genetically Modified Mesenchymal Stromal Cells.

Stem cells and development

Lenka Toro, Roman Bohovic, Miroslava Matuskova, Bozena Smolkova, Lucia Kucerova

Affiliations

  1. 1 Laboratory of Molecular Oncology, Cancer Research Institute , Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia .
  2. 2 Department of Genetics, Cancer Research Institute , Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia .

PMID: 27539058 DOI: 10.1089/scd.2016.0064

Abstract

Due to late diagnosis, often recurrence, formation of metastases and resistance to commonly used chemotherapeutics human ovarian carcinoma represents a serious disease with high mortality. Adipose tissue-derived mesenchymal stromal cells (AT-MSC) can serve as vehicles for therapeutic genes and we engineered AT-MSC to express either Herpes simplex virus thymidine kinase (HSVtk-MSC), which phosphorylates ganciclovir (GCV) to its toxic metabolites or yeast fused cytosine deaminase::uracil phosphoribosyltransferase (CD::UPRT-MSC), which converts 5-fluorocytosine (5-FC) to highly toxic 5-fluorouracil (5-FU). Here, we reported different responses of cytotoxicity mediated by CD::UPRT-MSC/5-FC treatment on human ovarian carcinoma cell lines-SKOV-3 and A2780 used in adherent or three-dimensional (3D) cell culture and we proved high potential of 3D model to predict results in our in vivo experiments. Both tumor cell lines showed similarly high chemosensitivity to the used treatment in adherent culture, but 3D model revealed severe discrepancy-only 36% of SKOV-3 cells but even 90% of A2780 cells were eliminated. This result served as a prognostic marker-we were able to achieve significantly decreased tumor volumes of subcutaneous xenografts of A2780 cells in nude mice and we prolonged tumor-free survival in 33% of animals bearing highly metastatic ovarian carcinoma after CD::UPRT-MSC/5-FC treatment.

Keywords: 5-fluorocytosine; adipose tissue-derived mesenchymal stromal cells; cancer gene therapy; cytosine deaminase; ovarian carcinoma

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