PURPOSE: 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.
PURPOSE: We have previously reported the expression of muscarinic acetylcholine receptors (mAChR) in humanbreast 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 cancerpatients 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 cancerpatients 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 cancerpatients 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: Alex I Chernyavsky; Vu Thuong Nguyen; Juan Arredondo; Assane Ndoye; Shaheen Zia; Jürgen Wess; Sergei A Grando Journal: Life Sci Date: 2003-03-28 Impact factor: 5.037
Authors: K Peraza-Cruces; L Gutiérrez-Guédez; D Castañeda Perozo; C R Lankford; C Rodríguez-Bonfante; R Bonfante-Cabarcas Journal: Braz J Med Biol Res Date: 2008-09 Impact factor: 2.590
Authors: María Gabriela Lombardi; María Pía Negroni; Laura Tatiana Pelegrina; María Ester Castro; Gabriel L Fiszman; María Eugenia Azar; Carlos Cresta Morgado; María Elena Sales Journal: PLoS One Date: 2013-02-27 Impact factor: 3.240