title: Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer.
abstract: BACKGROUND
  The re-emergence of the tumour growth factor-beta (TGF-beta)-related embryonic morphogen Nodal has recently been reported in several different human cancers. In this study, we examined the expression of Nodal in a series of benign and malignant human breast tissues to determine the clinical significance of this expression and whether Nodal could represent a potential therapeutic target in breast cancer.
  
  
  METHODS
  Tissue sections from 431 therapeutically naive patients diagnosed with benign or malignant breast disease were stained for Nodal by immunohistochemistry and analysed in a blinded manner. The degree of Nodal staining was subsequently correlated with available clinical data, such as diagnoses and disease stage. These tissue findings were further explored in breast cancer cell lines MDA-MB-231 and MDA-MB-468 treated with a Nodal blocking antibody to determine biological effects for target validation.
  
  
  RESULTS
  A variable degree of Nodal staining was detected in all samples. The intensity of Nodal staining was significantly greater in undifferentiated, advanced stage, invasive breast cancer compared with benign breast disease or early stage breast cancer. Treatment of human breast cancer cells in vitro with Nodal blocking antibody significantly reduced proliferation and colony-forming ability in soft agar, concomitant with increased apoptosis.
  
  
  CONCLUSIONS
  These data suggest a potential role for Nodal as a biomarker for disease progression and a promising target for anti-Nodal therapy in breast cancer.
authors.affiliation: Children's Memorial Research Center, Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 2300 Children's Plaza, Chicago, IL 60614, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Strizzi
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Hardy
authors.forename: Naira V
authors.initials: NV
authors.lastname: Margaryan
authors.forename: David W
authors.initials: DW
authors.lastname: Hillman
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Seftor
authors.forename: Beiyun
authors.initials: B
authors.lastname: Chen
authors.forename: Xochiquetzal J
authors.initials: XJ
authors.lastname: Geiger
authors.forename: E Aubrey
authors.initials: EA
authors.lastname: Thompson
authors.forename: Wilma L
authors.initials: WL
authors.lastname: Lingle
authors.forename: Cathy A
authors.initials: CA
authors.lastname: Andorfer
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Mary J C
authors.initials: MJ
authors.lastname: Hendrix
mesh_terms: D000328:Adult; D000368:Aged; D019138:Antibodies, Blocking / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D055457:Nodal Protein / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis
chemical_list: D019138:Antibodies, Blocking; D014408:Biomarkers, Tumor; C526007:NODAL protein, human; D055457:Nodal Protein