CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Autoantibodies from breast cancer patients regulate adhesion in MCF-7 human breast adenocarcinoma cells byactivation of muscarinic acetylcholine receptors
Autor/es:
PELEGRINA LT; FISZMAN G,; LOMBARDI G,; AZAR ME,; CRESTA MORGADO C,; SALES ME
Lugar:
Buenos Aires
Reunión:
Congreso; First French Argentine Immunology Congress; 2010
Institución organizadora:
Sociedad Argentina de Inmunologia-Sociedad Francesa de Inmunologia
Resumen:
Muscarinic acetylcholine receptors (mAChR) are expressed in
human breast tumor tissue and in MCF-7 cells, a human mammary
adenocarcinoma cell line, while they are absent in normal
mammary cells, MCF-10A. We described the presence of antimAChR
antibodies (Abs) in the sera of breast cancer patients in
stage 1 (T1N0Mx: tumor diameter<2cm, without lymph node
w.transbiomedicine.com
metastasis). We have demonstrated that the muscarinic agonist
carbachol (CARB) stimulated tumor cell proliferation and migration.
Metastases are the first cause of death in cancer and it occurs
when cells lose adhesion and migrate to distant organs.
The aim of this work is to investigate the role of mAChR activation
by CARB or T1NoMx-Abs on MCF-7 cells adhesion in an
in vitro assay. We demonstrated that CARB inhibited tumor cell
adhesion in a concentration dependent-manner, being 10-10M
the maximal effective concentration (25.6 } 0.97 %; p<0.001 vs.
basal). Pre-incubation of cells with atropine (AT: 10-9M) a non
selective muscarinic antagonist, 4-diphenylacetoxy-N-methylpiperidine
methiodide (4-DAMP: 10-9M) a selective antagonist
for mAChR3 or tropicamide (TROP: 10-9M) a selective antagonist
mAChR4, reverted the inhibition produced by CARB. In addition
we observed that T1N0Mx-Abs from 5 patients with breast cancer
mimicked the action of CARB producing a concentrationdependent
inhibition in MCF-7 cells adhesion, being 10-8M the
maximal effective concentration. The inhibition produced by
T1N0Mx-Abs ranged from 16.71}3.4 % to 40.19}8.8 % (p<0.001
vs. basal). These effects were always reverted with AT and TROP
but 4-DAMP was only effective to reduce Abs action in 3 of 5
patientes. CARB or Abs did not modify MCF-10A cells adhesion.
IgG from normal patients or with mammary benign fribroadenoma,
did not modify MCF-7 cells adhesion. We can conclude
that anti-mAChR Abs present in breast cancer patients sera at
early stages by stimulating migration and inhibiting adhesion
could be promoting breast cancer metastases.