Westbury, CB, Freeman, A, Rashid, M et al. (3 more authors) (2014) Changes in mast cell number and stem cell factor expression in human skin after radiotherapy for breast cancer. Radiotherapy and Oncology, 111 (2). 206 - 211. ISSN 0167-8140
Abstract
Background and purpose: Mast cells are involved in the pathogenesis of radiation fibrosis and may be a therapeutic target. The mechanism of increased mast cell number in relation to acute and late tissue responses in human skin was investigated. Materials and methods: Punch biopsies of skin 1 and 15–18 months after breast radiotherapy and a contralateral control biopsy were collected. Mast cells were quantified by immunohistochemistry using the markers c-Kit and tryptase. Stem cell factor (SCF) and collagen-1 expression was analysed by qRT-PCR. Clinical photographic scores were performed at post-surgical baseline and 18 months and 5 years post-radiotherapy. Primary human dermal microvascular endothelial cell (HDMEC) cultures were exposed to 2 Gy ionising radiation and p53 and SCF expression was analysed by Western blotting and ELISA. Results: Dermal mast cell numbers were increased at 1 (p = 0.047) and 18 months (p = 0.040) using c-Kit, and at 18 months (p = 0.024) using tryptase immunostaining. Collagen-1 mRNA in skin was increased at 1 month (p = 0.047) and 18 months (p = 0.032) and SCF mRNA increased at 1 month (p = 0.003). None of 16 cases scored had a change in photographic appearance at 5 years, compared to baseline. SCF expression was not increased in HDMECs irradiated in vitro. Conclusions: Increased mast cell number was associated with up-regulated collagen-1 expression in human skin at early and late time points. This increase could be secondary to elevated SCF expression at 1 month after radiotherapy. Although mast cells accumulate around blood vessels, no endothelial cell secretion of SCF was seen after in vitro irradiation. Modification of mast cell number and collagen-1 expression may be observed in skin at 1 and 18 months after radiotherapy in breast cancer patients with no change in photographic breast appearance at 5 years.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Mast cell; Photographic breast appearance; Radiation fibrosis; Stem cell factor |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Oncology and Clinical Research (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Mar 2015 15:40 |
Last Modified: | 20 Mar 2015 15:40 |
Published Version: | http://dx.doi.org/10.1016/j.radonc.2014.02.020 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.radonc.2014.02.020 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:83617 |