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Supportive Care in Cancer
Published in: Supportive Care in Cancer 4/2016

01-04-2016 | Original Article

Tight junction defects are seen in the buccal mucosa of patients receiving standard dose chemotherapy for cancer

Authors: Hannah R. Wardill, Richard M. Logan, Joanne M. Bowen, Ysabella Z. A. Van Sebille, Rachel J. Gibson

Published in: Supportive Care in Cancer | Issue 4/2016

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Abstract

Purpose

Oral mucositis is one of the most common and debilitating side effects of chemotherapy treatment. Patients are often unable to eat and drink, which can lead to poor clinical outcomes and extensive resource utilisation. The primary aim of this study was to determine the molecular integrity of oral epithelial tight junctions in patients undergoing chemotherapy. The secondary aim was to correlate these changes with proinflammatory cytokines and matrix metalloproteinase profiles.

Methods

Patients (n = 23) were recruited from the Royal Adelaide Hospital between 2000 and 2003. Reach patient underwent two oral buccal mucosa biopsies (4 mm): one prior to chemotherapy treatment and a second one after chemotherapy treatment. Oral buccal mucosa biopsies were also taken from seven healthy volunteers with no history of cancer, chemo- or radiotherapy treatment or inflammatory disorders. Routine haematoxylin and eosin staining was performed to determine epithelial thickness. Immunohistochemical staining was performed for claudin-1, zonular occludens-1, occludin, interleukin-1β, tumour necrosis factor, interleukin-6, matrix metalloproteinase-2 and metalloproteinase-9.

Results

Patients receiving standard dose chemotherapy had significant epithelial atrophy. Elevations in all cytokines and matrix metalloproteinases were seen, with significant lamina propria staining for interleukin-6 and tumour necrosis factor. Matrix metalloproteinase-2 appeared most upregulated within the oral epithelium. These changes coincided with altered tight junction staining properties. Changes in the staining intensity and localisation were both noted, with clear cytoplasmic staining for zonular occludens-1 and claudin-1 in patients treated with chemotherapy.

Conclusions

Chemotherapy causes defects in oral tight junctions, coupled with altered cytokine and matrix metalloproteinase profiles. Tight junction disruption in the epithelium may contribute to ulcer development or lead to poor tissue integrity, and the timing of these events may be a target for preventative treatment.
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Metadata
Title
Tight junction defects are seen in the buccal mucosa of patients receiving standard dose chemotherapy for cancer
Authors
Hannah R. Wardill
Richard M. Logan
Joanne M. Bowen
Ysabella Z. A. Van Sebille
Rachel J. Gibson
Publication date
01-04-2016
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 4/2016
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-015-2964-6

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