Muscarinic receptors as oncogenic proteins and targets of breast cancer treatment

SALEM A; SANCHEZ F; MARTINEZ PULIDO P; ESPAÑOL A; SALES M E; SANCHEZ Y

Valencia

Conferencia; 3rd Global Insight Conference on Breast Cancer; 2018

It has been thoroughly documented that the non-Neuronal Cholinergic System (nNCS) controls cancer progression. Particularly, we have demonstrated that muscarinic acetylcholine receptors (mAChRs), as components of the nNCS are involved in breast cancer progression in different experimental models. In mice, we demonstrated that mAChRs are expressed in 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 MCF-7 and MDA-MB-231. To analyze the role of mAChRs in human breast oncogenesis, we transfected the non-tumorigenic mammary cell line, MCF-10A which does not express mAChRs with these receptors and obtained stable clones. These clones formed spheroidal structures in vitro resembling tumor cells and responded to the stimulation with carbachol. Similar results were observed when we analyze their 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 with carbachol at low concentrations to murine breast cancer cells promotes cell lysis, mainly via apoptosis, we analyzed the role of mAChRs 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 (46±5% and 27±3% (p