title: Human lung cancer cells express functionally active Toll-like receptor 9.
abstract: BACKGROUND
  CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology.
  
  
  METHODS
  The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, in situ hybridization, RT-PCR and DNA-sequencing. Apoptosis and chemokine expression was detected by FACS analysis and the Bio-Plex system.
  
  
  RESULTS
  We found high TLR9 signal intensities in the cytoplasm of tumor cells in the majority of lung cancer specimens as well as in all tested tumor cell lines. In contrast to this non-malignant lung tissues showed only sporadically weak expression. Stimulation of HeLa and A549 cells with CpG-ODN induced secretion of monocyte chemoattractant protein-1 and reduction of spontaneous and tumor necrosis factor-alpha induced apoptosis.
  
  
  CONCLUSIONS
  Here we show that TLR9 is expressed in a selection of human lung cancer tissues and various tumor cell lines. The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology.
authors.affiliation: Medical Clinic, Research Center Borstel, D-23845 Borstel, Germany. ddroemann@fz-borstel.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Droemann
authors.forename: Dirk
authors.initials: D
authors.lastname: Albrecht
authors.forename: Johannes
authors.initials: J
authors.lastname: Gerdes
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
authors.forename: Detlev
authors.initials: D
authors.lastname: Branscheid
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Vollmer
authors.forename: Klaus
authors.initials: K
authors.lastname: Dalhoff
authors.forename: Peter
authors.initials: P
authors.lastname: Zabel
authors.forename: Torsten
authors.initials: T
authors.lastname: Goldmann
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D051217:Toll-Like Receptor 9