Chaoling Yao1, Yue Zhou2, Hui Wang2, Feiyan Deng3, Yongyi Chen4, Xiaomei Zhu4, Yu Kong5, Lijun Pan5, Lei Xue6, Xiao Zhou1, Chunmeng Shi7, Xiaowu Sheng8. 1. Department of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Tongzipo Road 283, Changsha, 410013, Hunan Province, China. 2. Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road 283, Changsha, 410013, Hunan Province, China. 3. Department of Radiotherapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Longgang District Baohe Avenue Road 113, Shenzhen, 518116, Guangdong Province, China. 4. Nursing Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Tongzipo Road 283, Changsha, 410013, Hunan Province, China. 5. Institute of Neuroscience, Chinese Academy of Sciences, 320, Yue Yang Road, Shanghai, 200031, China. 6. Pathology Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Tongzipo Road 283, Changsha, 410013, Hunan Province, China. 7. Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, No. 30, Main Street, Gaotanyan, Shapingba District, Chongqing, 400038, China. 8. Department of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Tongzipo Road 283, Changsha, 410013, Hunan Province, China. shengxiaowu789@163.com.
Abstract
BACKGROUND: Radiation-induced dermatitis is a serious side effect of radiotherapy, and very few effective treatments are currently available for this condition. We previously demonstrated that apoptosis is an important feature of radiation-induced dermatitis and adipose-derived stem cells (ADSCs) are one of the most promising types of stem cells that have a protective effect on acute radiation-induced dermatitis. Cathepsin F (CTSF) is a recently discovered protein that plays an important role in apoptosis. In this study, we investigated whether ADSCs affect chronic radiation-induced dermatitis, and the underlying mechanisms involved. METHODS: ADSCs were isolated from male Sprague-Dawley (SD) rats and characterized. For in vivo studies, rats were randomly divided into control and ADSC-treated groups, and cultured ADSCs were transplanted into radiation-induced dermatitis model rats. The effects of ADSC transplantation were determined by skin damage scoring, histopathological analysis, electron microscopy, immunohistochemical staining, and western blotting analysis of apoptosis-related proteins. To evaluate the effects of ADSCs in vitro, radiation-induced apoptotic cells were treated with ADSC culture supernatant, and apoptosis-related protein expression was investigated by TUNEL staining, flow cytometry, and western blotting. RESULTS: In the in vivo studies, skin damage, inflammation, fibrosis, and apoptosis were reduced and hair follicle and sebaceous gland regeneration were enhanced in the ADSC group compared with the control group. Further, CTSF and downstream pro-apoptotic proteins (Bid, BAX, and caspase 9) were downregulated, while anti-apoptotic proteins (Bcl-2 and Bcl-XL) were upregulated. In vitro, ADSCs markedly attenuated radiation-induced apoptosis, downregulated CTSF and downstream pro-apoptotic proteins, and upregulated anti-apoptotic proteins. CONCLUSION: ADSCs protect against radiation-induced dermatitis by exerting an anti-apoptotic effect through inhibition of CTSF expression. ADSCs may be a good therapeutic candidate to prevent the development of radiation-induced dermatitis.
BACKGROUND: Radiation-induced dermatitis is a serious side effect of radiotherapy, and very few effective treatments are currently available for this condition. We previously demonstrated that apoptosis is an important feature of radiation-induced dermatitis and adipose-derived stem cells (ADSCs) are one of the most promising types of stem cells that have a protective effect on acute radiation-induced dermatitis. Cathepsin F (CTSF) is a recently discovered protein that plays an important role in apoptosis. In this study, we investigated whether ADSCs affect chronic radiation-induced dermatitis, and the underlying mechanisms involved. METHODS: ADSCs were isolated from male Sprague-Dawley (SD) rats and characterized. For in vivo studies, rats were randomly divided into control and ADSC-treated groups, and cultured ADSCs were transplanted into radiation-induced dermatitis model rats. The effects of ADSC transplantation were determined by skin damage scoring, histopathological analysis, electron microscopy, immunohistochemical staining, and western blotting analysis of apoptosis-related proteins. To evaluate the effects of ADSCs in vitro, radiation-induced apoptotic cells were treated with ADSC culture supernatant, and apoptosis-related protein expression was investigated by TUNEL staining, flow cytometry, and western blotting. RESULTS: In the in vivo studies, skin damage, inflammation, fibrosis, and apoptosis were reduced and hair follicle and sebaceous gland regeneration were enhanced in the ADSC group compared with the control group. Further, CTSF and downstream pro-apoptotic proteins (Bid, BAX, and caspase 9) were downregulated, while anti-apoptotic proteins (Bcl-2 and Bcl-XL) were upregulated. In vitro, ADSCs markedly attenuated radiation-induced apoptosis, downregulated CTSF and downstream pro-apoptotic proteins, and upregulated anti-apoptotic proteins. CONCLUSION: ADSCs protect against radiation-induced dermatitis by exerting an anti-apoptotic effect through inhibition of CTSF expression. ADSCs may be a good therapeutic candidate to prevent the development of radiation-induced dermatitis.
Authors: Rebecca K S Wong; René-Jean Bensadoun; Christine B Boers-Doets; Jane Bryce; Alexandre Chan; Joel B Epstein; Beth Eaby-Sandy; Mario E Lacouture Journal: Support Care Cancer Date: 2013-08-14 Impact factor: 3.603
Authors: Philip J Coates; M Virginia C L Appleyard; Karen Murray; Caroline Ackland; June Gardner; Douglas C Brown; Dougal J A Adamson; Lee B Jordan; Colin A Purdie; Alastair J Munro; Eric G Wright; John A Dewar; Alastair M Thompson Journal: Cancer Res Date: 2010-11-16 Impact factor: 12.701