Expression and role of nestin in human cervical intraepithelial neoplasia and cervical cancer

Int J Oncol. 2012 Aug;41(2):441-8. doi: 10.3892/ijo.2012.1473. Epub 2012 May 10.

Abstract

Nestin expression reportedly correlates with aggressive growth, metastasis, poor prognosis and presence of cancer stem cells (CSCs) in various tumors. In this study, we determined the expression and role of nestin in cervical intraepithelial neoplasia (CIN) and cervical cancer. We performed immunohistochemical and in situ hybridization analyses of nestin in 26 cases for each stage of CIN and 55 cervical cancer tissue samples. To examine the role of nestin in cervical cancer cells, we stably transfected expression vectors containing nestin cDNA into ME-180 cells. We studied the effects of increased nestin expression on cell proliferation, cell motility, invasion as well as sphere and soft agar formation. Nestin was not localized in the squamous epithelium in normal cervical tissues, but it was weakly expressed in the basal squamous epithelium of CIN 1. In CIN 2, nestin was localized to the basal to lower 2/3 of the squamous epithelium, whereas in CIN 3, it was localized to the majority of the squamous epithelium. Nestin was detected in all cases of invasive cervical cancer. Nestin mRNA was expressed in both ME-180 and CaSki cells. Growth rate, cell motility and invasion ability of stably nestin-transfected ME-180 cells were not different from empty vector-transfected ME-180 (mock cells). However, the nestin-transfected ME-180 cells formed more colonies and spheres compared to the mock cells. These findings suggest that nestin plays important roles in carcinogenesis and tumor formation of cervical cancer cells. Nestin may closely correlate with regulation of CSCs.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cervical Intraepithelial Neoplasia / metabolism*
  • Cervical Intraepithelial Neoplasia / pathology
  • Female
  • Gene Expression
  • Humans
  • In Situ Hybridization
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism*
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nestin
  • Spheroids, Cellular / metabolism
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Intermediate Filament Proteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nestin