Cytoplasmic NANOG-positive stromal cells promote human cervical cancer progression

Am J Pathol. 2012 Aug;181(2):652-61. doi: 10.1016/j.ajpath.2012.04.008. Epub 2012 Jun 6.


Tumor development has long been known to resemble abnormal embryogenesis. The embryonic stem cell gene NANOG, a divergent homeodomain transcription factor that is independent of leukemia inhibitory factor, has been reported to be expressed in germ cells and in several tumor types. However, the short-term expression and role of NANOG in cervical cancer remain unclear. In the present study, we demonstrate that NANOG exhibits cellular shuttling behavior and increasing stromal distribution during the progression of cervical cancer. Our molecular data using RT-PCR and restriction enzyme digestion show that NANOG is mainly transcribed from the NANOG gene in cervical cancer. In addition, IHC using confocal microscopy suggests that mesenchymal stem cells (MSCs) are one type of cytoplasmic NANOG-positive cells in cervical cancer stroma. Co-culture of cervical cancer-derived MSCs with SiHa cells showed increased proliferation characteristics in vitro and enhanced tumor growth in vivo. Our results show, for the first time to our knowledge, that MSCs are a source of cytoplasmic NANOG expression in the cervical cancer stroma and that they participate in the progression of cervical cancer both in vitro and in vivo. Our study provides evidence that NANOG is a cervical cancer progression marker and also serves as a starting point for a more extensive exploration of the cellular translocation of NANOG and the multifunctionality of the stromal microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cell Line, Tumor
  • Cell Separation
  • Cytoplasm / metabolism*
  • Cytoplasm / pathology
  • Disease Progression*
  • Endoglin
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Mice
  • Nanog Homeobox Protein
  • Receptors, Cell Surface / metabolism
  • Reproducibility of Results
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Transcription, Genetic
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*
  • Xenograft Model Antitumor Assays


  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • Homeodomain Proteins
  • Hyaluronan Receptors
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Receptors, Cell Surface