title: Iroquois homeobox 2 suppresses cellular motility and chemokine expression in breast cancer cells.
abstract: BACKGROUND
  Disseminated tumor cells (DTCs) can be detected using ultrasensitive immunocytochemical assays and their presence in the bone marrow can predict the subsequent occurrence of overt metastasis formation and metastatic relapse. Using expression profiling on early stage primary breast tumors, low IRX2 expression was previously shown to be associated with the presence of DTCs in the bone marrow, suggesting a possible role of IRX2 in the early steps of metastasis formation. The purpose of this study is to gain insights into the significance of IRX2 protein function in the progression of breast cancer.
  
  
  METHODS
  To assess the physiological relevance of IRX2 in breast cancer, we evaluated IRX2 expression in a large breast cancer cohort (n = 1992). Additionally, constitutive IRX2 over expression was established in BT-549 and Hs578T breast cancer cell lines. Subsequently we analyzed whether IRX2 overexpression effects chemokine secretion and cellular motility of these cells.
  
  
  RESULTS
  Low IRX2 mRNA expression was found to correlate with high tumor grade, positive lymph node status, negative hormone receptor status, and basal type of primary breast tumors. Also in cell lines low IRX2 expression was associated with mainly basal breast cancer cell lines. The functional studies show that overexpression of the IRX2 transcription factor in basal cell lines suppressed secretion of the pro-metastatic chemokines and inhibited cellular motility but did not influence cell proliferation.
  
  
  CONCLUSIONS
  Our results imply that the IRX2 transcription factor might represent a novel metastasis associated protein that acts as a negative regulator of cellular motility and as a repressor of chemokine expression. Loss of IRX2 expression could therefore contribute to early hematogenous dissemination of breast cancer by sustaining chemokine secretion and enabling mobilization of tumor cells.
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. st.werner@uke.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Werner
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. h.stamm@uke.de.
authors.forename: Hauke
authors.initials: H
authors.lastname: Stamm
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. m.pandjaitan@uke.de.
authors.forename: Mutiha
authors.initials: M
authors.lastname: Pandjaitan
authors.affiliation: European Laboratory Association, Ibbenbüren, Germany. d.kemming@eurolabass.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Kemming
authors.affiliation: Department of Applied Bioinformatics (G200), German Cancer Research Center (DKFZ), Heidelberg, Germany. b.brors@dkfz-heidelberg.de.|National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany. b.brors@dkfz-heidelberg.de.|German Consortium for Translational Cancer Research (DKTK), 69120, Heidelberg, Germany. b.brors@dkfz-heidelberg.de.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. pantel@uke.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. h.wikman@uke.de.
authors.forename: Harriet
authors.initials: H
authors.lastname: Wikman
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018925:Chemokines; D018398:Homeodomain Proteins; C501595:IRX2 protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors