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MSC.sTRAIL Has Better Efficacy than MSC.FL-TRAIL and in Combination with AKTi Blocks Pro-Metastatic Cytokine Production in Prostate Cancer Cells

1
Cancer and Stem Cell Biology Group, School of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK
2
Molecular Oncology Group, School of Biological Sciences, University of Essex, Colchester CO4 3SQ, UK
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(4), 568; https://doi.org/10.3390/cancers11040568
Received: 4 March 2019 / Revised: 9 April 2019 / Accepted: 18 April 2019 / Published: 21 April 2019
(This article belongs to the Special Issue TRAIL Signaling in Cancer Cells)
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Abstract

Cell therapy is a promising new treatment option for cancer. In particular, mesenchymal stem cells (MSCs) have shown potential in delivering therapeutic genes in various tumour models and are now on the verge of being tested in the clinic. A number of therapeutic genes have been examined in this context, including the death ligand TRAIL. For cell therapy, it can be used in its natural form as a full-length and membrane-bound protein (FL-TRAIL) or as an engineered version commonly referred to as soluble TRAIL (sTRAIL). As to which is more therapeutically efficacious, contradicting results have been reported. We discovered that MSCs producing sTRAIL have significantly higher apoptosis-inducing activity than cells expressing FL-TRAIL and found that FL-TRAIL, in contrast to sTRAIL, is not secreted. We also demonstrated that TRAIL does induce the expression of pro-metastatic cytokines in prostate cancer cells, but that this effect could be overcome through combination with an AKT inhibitor. Thus, a combination consisting of small-molecule drugs specifically targeting tumour cells in combination with MSC.sTRAIL, not only provides a way of sensitising cancer cells to TRAIL, but also reduces the issue of side-effect-causing cytokine production. This therapeutic strategy therefore represents a novel targeted treatment option for advanced prostate cancer and other difficult to treat tumours. View Full-Text
Keywords: mesenchymal stem cells; cell therapy; sTRAIL; prostate cancer; AKT; AKTi; IL-6; CXCL5; ENA-78 mesenchymal stem cells; cell therapy; sTRAIL; prostate cancer; AKT; AKTi; IL-6; CXCL5; ENA-78
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Mohr, A.; Chu, T.; Brooke, G.N.; Zwacka, R.M. MSC.sTRAIL Has Better Efficacy than MSC.FL-TRAIL and in Combination with AKTi Blocks Pro-Metastatic Cytokine Production in Prostate Cancer Cells. Cancers 2019, 11, 568.

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