activity is modulated by auto-antibodies from breast cancer patients in MCF-7 cells

NEGRONI MARIA PÍA; FISZMAN GABRIEL; AZAR MARIA EUGENIA; CRESTA MORGADO CARLOS; ESPAÑOL ALEJANDRO; PELEGRINA LAURA TATIANA; DE LA TORRE EULALIA; SALES MARIA ELENA

J Clin Immunol

Springer Link

Año: 2010

Introduction  Muscarinic acetylcholine receptors (mAChR) belong to the G-protein-coupled receptor family and are extensively expressed in most cells in mammals. We had reported the expression of mAChR in murine and human breast tumors. Methods  The presence of antibodies in the sera of patients with different tumors directed against self-proteins has been recently described. In this work, we investigated the presence of autoantibodies against mAChR in the sera of breast cancer patients in stage I (T1N0Mx-IgG). IgG purification was performed by affinity chromatography in protein G-agarose. We also studied the ability of these antibodies to modulate the proliferation of MCF-7 breast tumor cells by the MTS colorimetric assay. The ability of T1N0Mx-IgG to stimulate muscarinic signaling pathway via nitric oxide synthase was tested by Griess reaction. Results  We demonstrated M3 and M4 receptors expression in MCF-7 cells. T1N0Mx-IgG promotes cell proliferation, mimicking the action of the muscarinic agonist carbachol. This effect was preferentially due to M3 receptor activation in tumor cells via phospholipase C-induced nitric oxide liberation by calcium-dependent nitric oxide synthases. IgG from control patients was unable to produce this effect. Discussion  IgG from patients with breast cancer in early stages could be promoting tumor progression by muscarinic activation, and its presence could be determining the prognosis of this illness.