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Upregulation of neutrophil gelatinase-associated lipocalin in oesophageal squamous cell carcinoma: significant correlation with cell differentiation and tumour invasion

Abstract

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family. Recently, an elevated NGAL expression was reported in several types of cancers. However, the characteristics of NGAL expression in oesophageal squamous cell carcinoma (ESCC) are still unknown.

Aim: To demonstrate the role of NGAL in ESCC.

Methods: NGAL expression in 81 paraffin sections, including ESCC, normal mucosa, simple hyperplasia and dysplasia, and in 73 fresh specimens of ESCC was analysed by immunohistochemistry, western blot and gelatin zymography.

Results: On immunohistochemical study, ESCC showed a diverse staining pattern for NGAL. However, only a weak positive signal was present within a restricted cytoplasmic area in the normal oesophageal epithelium. In dysplasia, altered NGAL expression could also be observed. On western blot study, NGAL expression level was found to be significantly higher in ESCC than in normal mucosa (p = 0.030), and to be positively correlated with cell differentiation. However, no significant association was observed between NGAL expression and cell proliferation. In addition, the enzymic activity of the NGAL/matrix metalloproteinase 9 complex was much higher in ESCC than in normal mucosa, and was significantly correlated with the depth of tumour invasion in zymography analysis (p = 0.006).

Conclusions: The findings suggest that NGAL is involved in the differentiation pathway and invasive progression of ESCC.

  • ESCC, oesophageal squamous cell carcinoma
  • MMP-9, matrix metalloproteinase 9
  • NGAL, neutrophil gelatinase-associated lipocalin
  • PBS, phosphate-buffered saline
  • PCNA, proliferating cell nuclear antigen

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