title: Association between ligands and receptors related to the progression of early breast cancer in tumor epithelial and stromal cells.
abstract: BACKGROUND
  Despite advances in the study of breast cancer (BC), it remains the second leading cause of mortality among women. BC is a heterogeneous system, mainly composed of tumor epithelial cells (TEpCs) and stromal cells (SCs); the interaction through the ligands and their receptors (Rs) plays a major role in BC progression. The aim of the present study was to evaluate the association between ligands, such as osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), receptor activator of nuclear factor kappa B ligand (RANKL), stromal cell-derived factor (SDF)-1, interleukin (IL)-6, macrophage colony stimulating factor, chemokine (C-C motif) ligand-2 (CCL-2), and their Rs in TEpC and spindle-shaped SCs not closely associated with the vasculature.
  
  
  METHODS
  We studied the expression of all those factors in 63 primary tumors of untreated patients with BC with infiltrative ductal carcinoma (I/II stage) and 10 non-neoplastic tissues. The percentage of positive cells and the staining intensity were analyzed by immunohistochemistry. Mann-Whitney test and Spearman's rank correlation coefficient were used (P ≤ .05).
  
  
  RESULTS
  We found a significant association between the expression of RANKL, IL-6, SDF-1, and CCL-2 in TEpC and the receptor activator of nuclear factor kappa B (RANK), IL-6R, C-X-C chemokine R type 4, and chemokine (C-C motif) R-2 (CCR-2) in spindle-shaped SC. The expression of TRAIL, RANKL, and CCL-2 in spindle-shaped SC also was associated with the expression of TRAIL-receptor 1, TRAIL-receptor 4, RANK, and CCR-2 in TEpC.
  
  
  CONCLUSIONS
  Because the described ligands and Rs are implicated in BC progression, our results suggest that these factors could be involved in the crosstalk between TEpC and SC in the early stages of BC.
authors.affiliation: Experimental Biology and Medicine Institute, National Council of Scientific and Technical Research, Buenos Aires, Argentina.
authors.forename: Vivian
authors.initials: V
authors.lastname: Labovsky
authors.affiliation: Experimental Biology and Medicine Institute, National Council of Scientific and Technical Research, Buenos Aires, Argentina.
authors.forename: Leandro Marcelo
authors.initials: LM
authors.lastname: Martinez
authors.affiliation: Department of Pathological Anatomy, Italian Hospital, Buenos Aires, Argentina.
authors.forename: Kevin Mauro
authors.initials: KM
authors.lastname: Davies
authors.affiliation: Department of Pathological Anatomy, Italian Hospital, Buenos Aires, Argentina.
authors.forename: Hernán
authors.initials: H
authors.lastname: García-Rivello
authors.affiliation: Department of Biostatistic, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: María de Luján
authors.initials: Mde L
authors.lastname: Calcagno
authors.affiliation: Experimental Biology and Medicine Institute, National Council of Scientific and Technical Research, Buenos Aires, Argentina.
authors.forename: Ayelén
authors.initials: A
authors.lastname: Matas
authors.affiliation: Experimental Biology and Medicine Institute, National Council of Scientific and Technical Research, Buenos Aires, Argentina.
authors.forename: Valeria Beatriz
authors.initials: VB
authors.lastname: Fernández Vallone
authors.affiliation: Department of Pathological Anatomy, Italian Hospital, Buenos Aires, Argentina.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Wernicke
authors.affiliation: Texas A&M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott & White, Temple, TX.
authors.forename: Hosoon
authors.initials: H
authors.lastname: Choi
authors.affiliation: Experimental Biology and Medicine Institute, National Council of Scientific and Technical Research, Buenos Aires, Argentina. Electronic address: alejachase@gmail.com.
authors.forename: Norma Alejandra
authors.initials: NA
authors.lastname: Chasseing
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D053245:RANK Ligand / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; C508600:IL6 protein, human; D015850:Interleukin-6; D008024:Ligands; D053245:RANK Ligand; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505688:TNFSF11 protein, human
keywords: Breast cancer; Ligands; Receptors; Stromal cells; Tumor epithelial cells