Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region.
Strahlenther Onkol
; 193(11): 951-960, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28812103
ABSTRACT
PURPOSE:
Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators osteopontin (OPN), regulated by sex-determining region Ybox 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. MATERIALS ANDMETHODS:
DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively.RESULTS:
DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels.CONCLUSION:
Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complicações Pós-Operatórias
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Arteríolas
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Lesões por Radiação
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Neoplasias Otorrinolaringológicas
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Proteínas de Homeodomínio
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Terapia Neoadjuvante
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Peptídeos e Proteínas de Sinalização Intercelular
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Osteopontina
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Fatores de Transcrição SOX9
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Retalho Perfurante
Limite:
Humans
Idioma:
En
Revista:
Strahlenther Onkol
Assunto da revista:
NEOPLASIAS
/
RADIOTERAPIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha