Radiation-Induced Bystander Effects of Adipose-Derived Mesenchymal Stem Cells

Document Type : Original Article

Authors

1 Ionizing and Non-ionizing Radiation Protection Research Center (INIRPRC), School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

2 Ionizing and Non-ionizing Radiation Protection Research Center (INIRPRC), School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran;. Department of Radio-oncology, Shiraz University of Medical S

3 Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;4Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

4 5Department of Medical Physics and Engineering, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Objective
The interaction of tumor cells with surrounding stem cells such as adipose-derived mesenchymal stem cells (ASCs) would be a crucial mechanism of tumor progression. It has been shown that irradiation can affect tumor microenvironment through different mechanisms. Given that, we aimed to examine the bystander radiation-induced effects of ASCs on different cancer cell lines.
Materials and Methods
In this experimental study, ASCs were extracted from five healthy donors, cultured and then irradiated with a 5Gy of gamma radiation. Following 72 hours of incubation, irradiated ASCs-conditioned media (IACM) and non-irradiated ASCs-conditioned media (NIACM) were collected. Following incubation of different cell lines, Jurkat, LNCaP, U87-MG, MDA-MB-231 and MCF-7, in different media, DMEM, NIACM, and IACM, ALDEFLUOR assay and wound healing assays, were conducted. Using quantitative real-time polymerase chain reaction (qRT-PCR), the expression of ATP-binding cassette transporter genes, ABCA1 and ABCG2, was measured in these cell lines.
Results
NIACM significantly increased ALDH activity in MDA-MB-231 cell (P=0.02), while IACM was associated with significant decrease in the LNCaP and MCF-7 cell lines, respectively P=0.02, P=0.03, compared to DMEM as the control. The area of the scratch site was significantly reduced in MDA-MB-231 cells cultured with NIACM compared to DMEM (P=0.04). Furthermore, ABCA1 mRNA expression was considerably decreased in IACM- but not in DMEMtreated LNCaP line (P=0.01).
Conclusion
It seems, after exposing to radiation, ASCs modify to prevent tumor development and metastasis through their radiation-induced bystander effects. Therefore, a better understanding of ASCs function in the tumor microenvironment may provide new insights into therapeutic strategies to surmount radio-resistance in cancer treatment.

Keywords