Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Downregulates the Expression of Protumor Factors Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in a GM-CSF Receptor-Independent Manner in Cervical Cancer Cells

Mediators Inflamm. 2015:2015:601604. doi: 10.1155/2015/601604. Epub 2015 Jul 15.

Abstract

Enhanced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) is associated with the pathogenic processes of various tumor types. COX-2 and iNOS expression in the immunomodulatory dendritic cells is mediated by the granulocyte macrophage-colony stimulating factor (GM-CSF), which is also expressed by cervical cancer cells; however, whether and how GM-CSF regulates COX-2 and iNOS expression in clinical cervical cancer cells remain unknown. In this study, we found that the COX-2 and iNOS expression was upregulated in the cervical cancer tissues and positively correlated with cancer metastasis and stage. About one-half of the cervical cancer tissues showed strong/moderate GM-CSF expression, while the normal cervical tissues showed >80% positive rate; no GM-CSFR protein was detectable on the cervical cancer cells. The GM-CSF expression was negatively correlated with the COX-2 and iNOS expression in the cervical cancer tissues and the functional negative regulatory effect of GM-CSF on COX-2/iNOS expression was demonstrated in various cervical cancer cell lines. Therefore, in cervical cancer cells, GM-CSF might contribute an antitumor response by inhibiting iNOS and COX-2 expression in a GM-CSFR independent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cyclooxygenase 2 / metabolism*
  • Down-Regulation / drug effects
  • Female
  • Gene Expression / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Middle Aged
  • Nitric Oxide Synthase Type II / metabolism*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Uterine Cervical Neoplasms / metabolism*

Substances

  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2