title: Breast cancer cell-derived cytokines, macrophages and cell adhesion: implications for metastasis.
abstract: BACKGROUND
  Liver metastasis is associated with a proinflammatory microenvironment and up-regulation of cell adhesion molecules expressed by endothelial cells. The aim of this study was to characterize the interrelations between breast cancer cell-secreted cytokines, macrophages and E-selectin-mediated cancer cell adhesion and their role in metastasis of breast cancer.
  
  
  METHODS
  Three metastatic breast cancer cell lines (1590, KM22, ZE) were studied. Cell culture supernatants were screened for cytokines and the potential for cytokines to increase tumor-necrosis factor-α (TNF-α) production by ANA-1-macrophages was analyzed. E-Selectin-mediated tumor cell adhesion of fluorescence labelled tumor cells was evaluated by measurement of fluorescence intensity with and without E-selectin-blocking strategies (monoclonal antibodies, cimetidine).
  
  
  RESULTS
  Tumor-specific cytokine secretion patterns were revealed. TNF-α secretion from cultured macrophages increased after incubation with tumor supernatants. Tumor cell adhesion was significantly inhibited by cimetidine and monoclonal antibodies against E-selectin (KM22 with cimetidine, p<0.05).
  
  
  CONCLUSIONS
  Breast cancer cell-secreted cytokines stimulate macrophages to produce TNF-α, a known up-regulator of E-selectin expression, and therefore cell adherence to endothelium. Inhibition of this mechanism could be an attractive therapeutic option for the prevention of breast cnacer metastasis.
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg Medical School, Voss-Strasse 9, D-69115 Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Eichbaum
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Meyer
authors.forename: Ni
authors.initials: N
authors.lastname: Wang
authors.forename: Esther
authors.initials: E
authors.lastname: Bischofs
authors.forename: Andrea
authors.initials: A
authors.lastname: Steinborn
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.forename: Pnina
authors.initials: P
authors.lastname: Brodt
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.forename: Michael H R
authors.initials: MH
authors.lastname: Eichbaum
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002927:Cimetidine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D019040:E-Selectin / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000473:pathology*; D012995:Solubility / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D002927:Cimetidine