Expression of Wnt-1, TGF-β and related cell-cell adhesion components following radiotherapy in salivary glands of patients with manifested radiogenic xerostomia

Radiother Oncol. 2011 Oct;101(1):93-9. doi: 10.1016/j.radonc.2011.07.032. Epub 2011 Aug 30.

Abstract

Background: Radiation-induced xerostomia still represents a common symptom following radiotherapy of head and neck malignancies, which significantly impairs the patient's quality of life. In this cross-sectional study, human salivary glands were investigated to assess the role of Wnt/β-catenin and TGF-β pathways in the pathogenic process of radiogenic impairment of salivary function.

Methods: Irradiated human salivary glands were investigated in patients with manifested xerostomia. Alteration of Wnt-1 and cell-cell adhesion was evaluated immunohistologically as well as changes in the expression of TGF-β were assessed in salivary gland tissue.

Results: We assessed two alteration patterns in which Wnt-1 expression represents one change along with up-regulation of β-catenin and E-cadherin in irradiated but viable acinar cells. Increased expression of tenascin-C was observed in sites of epithelial-mesenchymal interaction and loss of cell-cell adhesion was assessed in translocated epithelial cells in the stroma.

Conclusion: Increased transdifferentiation and remodeling of acinar structures was associated with decrease of viable acinar structures. The role of Wnt and TGF signaling may provide a potential therapeutic approach to prevent radiation-induced damage to salivary glands during radiotherapy for head and neck cancer.

Publication types

  • Comparative Study

MeSH terms

  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cross-Sectional Studies
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Immunohistochemistry
  • Male
  • Prognosis
  • Radiotherapy / adverse effects*
  • Radiotherapy Dosage
  • Risk Assessment
  • Salivary Gland Neoplasms / pathology
  • Salivary Gland Neoplasms / radiotherapy
  • Salivary Glands / pathology
  • Salivary Glands / radiation effects*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Treatment Outcome
  • Up-Regulation
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism*
  • Xerostomia / etiology*
  • Xerostomia / metabolism*
  • Xerostomia / pathology

Substances

  • Cadherins
  • Cell Adhesion Molecules
  • Transforming Growth Factor beta
  • Wnt1 Protein