Abstract
Purpose
Chemotherapy-induced mucositis is characterised by damage to mucous membranes throughout the alimentary tract. This study aims to investigate the expression of cell adhesion molecules (CAMs) following treatment with irinotecan.
Methods
Dark agouti rats received a single dose of 175 mg/kg irinotecan and sacrificed at various time points after treatment. Picro-sirius red staining indicated an increase in collagen around crypts from 24 h in both small and large intestinal regions and this diminished at the later time points. CAMs E-cadherin, P-selectin, E-selectin and integrin-α1 were examined using immunohistochemistry.
Results
E-cadherin was significantly elevated in jejunal crypts at the time of maximal tissue damage (48 h), while it decreased at the healing phase (96 h) in both jejunum and colon. P-selectin expression decreased significantly in the jejunum following irinotecan. Crypt expression of E-selectin was significantly elevated in the healing phase of mucositis (96 h). Integrin-α1 expression was significantly altered during the time course in the villus (p = 0.0032) and lamina propria (p = 0.039).
Conclusions
Irinotecan induced a significant alteration in CAM expression in the jejunum and colon. Changes in adhesion molecule expression may have a direct impact on the loss of mucosal layer integrity seen in mucositis.
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All experimental procedures were approved by the Animal Ethics Committees of the Institute of Medical and Veterinary Sciences and the University of Adelaide and complied with the National Health and Medical Research Council (Australia) Code of Practice for Animal Care in Research and Training (2004).
Conflict of interest
Dr. Noor Al-Dasooqi was supported by a Postgraduate Research Fellowship from the Centre for Clinical Research Excellence; Dr. Joanne M Bowen was supported by a Postdoctoral Research Fellowship from the National Health and Medical Research Council; Professor Dorothy Keefe is the Cancer Council SA Chair of Cancer Medicine; and A/Prof Rachel J Gibson received funding from Cure Cancer and Cancer Australia. Assistance with the statistical analysis for this study was provided by Mr. Thomas Sullivan from the Department of Public Health, The University of Adelaide. There are no conflicts of interest to declare. The authors have full control of all primary data and we allow the journal to review the data if requested.
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Al-Dasooqi, N., Bowen, J., Bennett, C. et al. Cell adhesion molecules are altered during irinotecan-induced mucositis: a qualitative histopathological study. Support Care Cancer 25, 391–398 (2017). https://doi.org/10.1007/s00520-016-3413-x
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DOI: https://doi.org/10.1007/s00520-016-3413-x