title: Immunoglobulin g from breast cancer patients regulates MCF-7 cells migration and MMP-9 activity by stimulating muscarinic acetylcholine receptors.
abstract: OBJECTIVE
  We have previously reported the expression of muscarinic acetylcholine receptors (mAChR) in human breast tumors. The activation of these receptors triggered tumor cell proliferation. Considering that invasion and metastasis is the major cause of death in cancer, we investigated the action of autoantibodies against mAChR derived from breast cancer patients in stage I (T1N0Mx-IgG) on MCF-7 cells migration and metalloproteinase-9 (MMP-9) activity. We also analyzed the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.
  
  
  METHODS
  Immunoglobulin G (IgG) was purified by chromatography in protein G-agarose from blood samples of breast cancer patients obtained under informed consent. Migration was assayed by an in vitro wound assay. MMP-9 activity was quantified by zymography.
  
  
  RESULTS
  T1N0Mx-IgG promoted tumor cell migration and increased MMP9 activity mimicking the action of the muscarinic agonist carbachol. This effect was reduced not only by the presence of atropine but also by 4-DAMP or tropicamide, antagonists for M(3) and M(4) mAChR subtypes respectively. The actions of T1N0Mx-IgG and carbachol on MCF-7 cells, involved the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.
  
  
  CONCLUSIONS
  IgG from breast cancer patients in stage I could be promoting tumor progression by regulating migration and MMP-9 activity in tumor cells via mAChR activation. The presence of these autoantibodies could be determining the prognosis of breast cancer in these patients.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos (CEFYBO)-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 piso 16, Buenos Aires, CP 1121, Argentina.
authors.forename: Laura T
authors.initials: LT
authors.lastname: Pelegrina
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Lombardi
authors.forename: Gabriel L
authors.initials: GL
authors.lastname: Fiszman
authors.forename: María E
authors.initials: ME
authors.lastname: Azar
authors.forename: Carlos Cresta
authors.initials: CC
authors.lastname: Morgado
authors.forename: María E
authors.initials: ME
authors.lastname: Sales
mesh_terms: D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D018679:Cholinergic Agonists / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000494:pharmacology; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001323:Autoantibodies; D018679:Cholinergic Agonists; D007074:Immunoglobulin G; D011976:Receptors, Muscarinic; D002217:Carbachol; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D054801:Phosphoinositide Phospholipase C; D020780:Matrix Metalloproteinase 9