CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Muscarinic acetylcholine receptors as a double edged sword. Their role in tumorigenesis and in breast cancer treatment
Autor/es:
ESPAÑOL A; LOMBARDI G,; MARTINEZ PULIDO P; SALEM A; SALES ME,
Lugar:
Giessen
Reunión:
Simposio; 4th International Symposium in non neuronal acetylcholine.; 2014
Resumen:
It has been thoroughly documented that the non Neuronal Cholinergic System (nNCS)
controls cancer progression. Particularly, we have demonstrated that muscarinic
acetylcholine receptors (mAChR), as components of the nNCS are involved in breast
cancer progression in different experimental models. In mice, we demonstrated that
mAChR are expressed in three distinct spontaneous mammary adenocarcinomas, while
they were absent in normal epithelial mammary cells. In humans, we detected the
expression of mAChR in breast tumor homogenates as well as, in two different tumor cell
lines MDA-MB-231 and in MCF-7. The latter exhibits a marked expression of 3 and 4
subtypes. To analyze the role of mChR in human breast oncogenesis, we transfected the
non tumorigenic mammary cell line, MCF-10A, which does not express mAChR with
these receptors and obtained three stable clones (MCF-10A-mAChR3, MCF-10AmAChR4
and MCF-10A-mAChR3&4). These clones formed spheroid structures in vitro
resembling MCF-7 cells and responded to the stimulation with carbachol. Similar results
were observed when we analyze tumor growth in NUDE mice. Untransfected MCF-10A
cells were unable to grow either in tridimensional culture or in NUDE mice. Taking into
account these previous results, as well as the fact that the addition of a combination of
paclitaxel plus carbachol at low concentrations to murine breast cancer cells promotes
tumor cell lysis, mainly via apoptosis, we analyzed the role of mAChR as therapeutic
targets in human breast cancer treatment. We confirmed that this combination was
equally useful to trigger cell death in MCF-7 and MDA-MB-231 human
adenocarcinomas, while it was innocuous in MCF-10A cells. These results let us
speculate, in the possibility of the use of this type of metronomic therapy in breast cancer.