Antibodies against muscarinic receptors in breast cancer patients.

MIDDONNO MARIA CRISTINA; FISZMAN GABRIEL; AZAR MARIA EUGENIA; CRESTA MORGADO C.; DE LA TORRE E; ESPAÑOL ALEJANDRO; NEGRONI MARIA PIA; SALES MARÍA ELENA

Rio de Janeiro, Brasil.

Congreso; VII Congress of the International Society for Neuroimmunomodulation.; 2008

International Society for Neuroimmunomodulation.

Introduction: we had  described autoantibodies (Ab) against muscarinic receptors (mAChR) in murine mammary adenocarcinoma bearing mice. These Ab stimulate tumor cell proliferation and angiogenesis. mAChR have been identified as target of humoral immune response in Sjögrem and HIV patients. We had previously reported that human mammary tumor tissue expressed mAChR that are absent in normal surrounding tissue. The addition of carbachol (CARB) (10-9M) a non selective muscarinic agonist, stimulates by 48% (p<0.05; n=8) MCF-7 cells proliferation, derived from a human mammary adenocarcinoma, via M3 receptor. Here we investigate the action of IgG purified 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. Methods: 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 lymph node metastases (T1N0Mx) stimulates by 50% (p<0.05; n=3) comparable to the action of 10-9M carbachol (CARB). The effect is significantly reduced  by 10-6 M atropine (AT). IgG from patients in stage II (T2N0Mx) increased MCF-7 cells proliferation by 40% (p<0.05; n=3) but this effect was not modified by AT. IgG from BFA did not modify MCF-7 cell duplication. Normal IgG stimulates tumor cell proliferation by 30% (p<0.05; n=4) and AT reduced by 50% this effect. Conclusion: there is a fraction of Ab with muscarinic activity in breast cancer patients in early tumor bearers that could promote tumor progression. Fundación Roemmers 2007-2008. UBACYT MO04.