Antibodies against muscarinic receptors in breast cancer patients

SALES MARÍA ELENA; MIDDONNO CRISTINA; FISZMAN GABRIEL; AZAR MARIO; CRESTA MARIO; DE LA TORRE EULALIA; ESPAÑOL ALEJANDRO; NEGRONI, PIA

Rio de Janeiro, Brasil

Congreso; VII ISNIM Congress. The International Society for NeuroImmunoModulation; 2008

Introduction: we had described that autoantibodies (Abs) against muscarinic receptors (mAChR) are present in murine mammary adenocarcinoma bearing mice. These Abs stimulate tumor cell proliferation and angiogenesis. mAChR have been identified as target of humoral immune response in Sjögren and HIV patients. We have recently reported that human mammary tumor tissue express mAChR that are absent in normal surrounding tissue. The addition of 10-9M carbachol (CARB) a non selective muscarinic agonist, stimulates by 48% (p<0.05; n=8) the proliferation of MCF-7 cells, derived from human breast adenocarcinoma, via M3 receptor. Here we investigate the action of IgG from breast cancer patients in stage I and II in comparison with IgG from benign fibroadenoma (BFA) or normal donors, on MCF-7 cells proliferation. Methodology: IgG was purified by affinity chromatography with protein A-Sepharose, MTT kit was used to test MCF-7 cell proliferation; protein expression was assayed by Western blot (Wb). Results: IgG from stage I patients without node metastases (T1N0Mx) stimulates by 50% (p<0.05; n=3) cell proliferation; similarly to 10-9M CARB. Both effects were reduced by 10-6M atropine (AT). IgG from patients in stage II (T2N0Mx) increased MCF-7 cells proliferation by 40% (p<0.05; n=3) but it was not modified by AT. IgG from BFA did not modify cell duplication. Normal IgG stimulates by 30% (p<0.05; n=3) MCF-7 cells growth and AT only reduced to half this effect. Conclusions: There is a faction of Abs with muscarinic activity in breast cancer patients at early stages that could be promoting tumor progression.