DistributionSubmit your manuscript at www.biomedcentral.com/submit

Kim et al.

DistributionSubmit your manuscript at www.biomedcentral.com/submit

Kim Rosiglitazone et al. Cell Bioscience 2015, 5:2 http://www.cellandbioscience.com/content/5/1/Cell BioscienceOpen AccessRESEARCHQuantitative proteomic analysis of single or fractionated radiation-induced proteins in human breast cancer MDA-MB-231 cellsMi-Hyoung Kim1,2, Seung-Youn Jung1, Jiyeon Ahn1, Sang-Gu Hwang1, Hee-Jong Woo2, Sungkwan An3, Seon Young Nam4, Dae-Seog Lim5 and Jie-Young Song1*AbstractBackground: Radiotherapy is widely used to treat cancer alone or in combination with surgery, chemotherapy, and immunotherapy. However, damage to normal tissues and radioresistance of tumor cells are major obstacles to successful radiotherapy. Furthermore, the immune network around tumors appears to be connected to tumor progression and recurrence. Methods: We investigated the cytosolic proteins produced by irradiated tumor cells by using a quantitative proteomic approach based on stable isotope labeling by amino acids in cell culture. MDA-MB-231 breast cancer cells were treated PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/15501003 with a single or fractionated 10 Gray dose of 137Cs -radiation, which was selected based on cell viability. Results: Radiation-induced proteins were differentially expressed based on the fractionated times of radiation and were involved in multiple biological functions, including energy metabolism and cytoskeleton organization. We identified 46 proteins increased by at least 1.3-fold, and high ranks were determined for cathepsin D, gelsolin, arginino-succinate synthase 1, peroxiredoxin 5, and C-type mannose receptor 2. Conclusion: These results suggest that a number of tumor-derived factors upregulated by -radiation are promising targets for modulation of the immune response during radiation treatment. Keywords: Breast cancer, Proteomics, Radiation therapy, SILACBackground Radiation therapy (RT) is one of the most common treatments for cancer and can be provided alone or, frequently, in combination with surgery, chemotherapy, or immunotherapy [1,2]. Depending on the type of cancer, 50?0 of cancer patients undergo RT during the course of their illness, with the highest percentages in cases of non-small-cell lung cancer, prostate, breast, and colon cancer [3,4]. However, RT is associated with acute or chronic side effects such as injury to normal tissues, fatigue, nausea/vomiting, diarrhea, and intestinal bleeding. The effect of radiation on tumor cells varies greatly* Correspondence: immu@kirams.re.kr Equal contributors 1 Division of Radiation Cancer Research, Korea Institute of Radiological Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul 139-706, Korea Full list of author information is available at the end of the articleaccording to the type of radiation, total dose, dose rate, and time of testing post-exposure [4-7]. Therefore, the reasons for RT failure are multiple and vary, and major causes include inadequate vascular supply (hypoxia), cancer stem cells, and novel mutations [8]. Furthermore, tumors can survive in complex systems, including heterogeneous tumor cells, tumor-associated cells, normal cells, and immune cells, rather than as a simple mass of malignant cells. Notably, tumor-associated immune cells produce various signals that are highly predictive of the efficiency of RT as well as cancer progression and recurrence [9]. In the last several years, stimulation of the immune system has been proposed to occur through immunogenic cell death (ICD) mediated mainly by danger signals from e.