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Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-? activated adipose derived mesenchymal stem cells in breast cancer model.

ABSTRACT: Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment in various types of cancer. Moreover, irradiation is usually applied as either a standard primary or adjuvant therapy. Here, we showed that the expression of TNF related apoptosis-inducing ligand (TRAIL) and Dickouf-3 (Dkk-3), the promising anticancer proteins, increased in murine adipose-derived mesenchymal stromal cells (AD-MSCs) following activation with TNF-?, resulting in the induction of apoptosis in cancer cells. Also, anticancer effects of TNF-? activated AD-MSCs were intensified with irradiation. In vivo results showed that TNF-? preactivated AD-MSCs combined with irradiation decreased tumor size and increased survival rate in tumor bearing mice. On the other hands, both TNF-? preactivated AD-MSCs with or without irradiation prevented metastasis in ling and liver, and increased apoptosis in tumor mass. Finally, flowcytometry assay demonstrated that naïve AD-MSCs combined with irradiation but not TNF-? activated MSCs with irradiation increased Treg population in lymph node and spleen. Altogether, obtained results suggest that TNF-? activated MSCs combined with irradiation therapy can serve as new strategy in breast cancer therapy.

SUBMITTER: Mohammadpour H

PROVIDER: S-EPMC4916474 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-α activated adipose derived mesenchymal stem cells in breast cancer model.

Mohammadpour Hemn H Pourfathollah Ali Akbar AA Nikougoftar Zarif Mahin M Shahbazfar Amir Ali AA

Scientific reports 20160622

Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment in various types of cancer. Moreover, irradiation is usually applied as either a standard primary or adjuvant therapy. Here, we showed that the expression of TNF related apoptosis-inducing ligand (TRAIL) and Dickouf-3 (Dkk-3), the promising anticancer proteins, increased in murine adipose-derived mesenchymal stromal cells (AD-MSCs) following activation with TNF-α, resulting in the induction of apoptos ...[more]

PMID: 27329316

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Project description:The objective of this study was to evaluate the effects of red Light Emiting Diode (red LED) irradiation on fibroblasts in adipose-derived mesenchymal stem cells (ASC) co-culture on the scratch assay. We hypothesized that red LED irradiation could stimulate paracrine secretion of ASC, contributing to the activation of genes and molecules involved in cell migration and tissue repair. ASC were co-cultured with NIH/3T3 fibroblasts through direct contact and subjected to red LED irradiation (1.45 J/cm2/5min6s) after the scratch assay, during 4 days. Four groups were established: fibroblasts (F), fibroblasts + LED (FL), fibroblasts + ASC (FC) and fibroblasts + LED + ASC (FLC). The analyzes were based on Ctgf and Reck expression, quantification of collagen types I and III, tenomodulin, VEGF, TGF-β1, MMP-2 and MMP-9, as well as viability analysis and cell migration. Higher Ctgf expression was observed in FC compared to F. Group FC presented higher amount of tenomodulin and VEGF in relation to the other groups. In the cell migration analysis, a higher number of cells was observed in the scratched area of the FC group on the 4th day. There were no differences between groups considering cell viability, Reck expression, amount of collagen types I and III, MMP-2 and TGF-β1, whereas TGF-β1 was not detected in the FC group and the MMP-9 in none of the groups. Our hypothesis was not supported by the results because the red LED irradiation decreased the healing response of ASC. An inhibitory effect of the LED irradiation associated with ASC co-culture was observed with reduction of the amount of TGF-β1, VEGF and tenomodulin, possibly involved in the reduced cell migration. In turn, the ASC alone seem to have modulated fibroblast behavior by increasing Ctgf, VEGF and tenomodulin, leading to greater cell migration. In conclusion, red LED and ASC therapy can have independent effects on fibroblast wound healing, but the combination of both does not have a synergistic effect. Therefore, future studies with other parameters of red LED associated with ASC should be tested aiming clinical application for tissue repair.

Dataset Information

Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-? activated adipose derived mesenchymal stem cells in breast cancer model.

Publications

Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-α activated adipose derived mesenchymal stem cells in breast cancer model.

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