NK1 receptor blockade disrupts microtumor growth and aggregation in a three-dimensional syngeneic breast cancer model

Abstract

Several data indicate that Substance P (SP) neurokinin type 1 receptor (NK1R) is at the center of the interaction between cancer cells and peripheral sensory neurons. Selecting the appropriate cancer cell line and its susceptibility to being modulated by NK1 antagonists are critical to studying this complex interaction. In the current study, we have focused on this selection by comparing several aspects of the allogeneic triple-negative breast cancer (TNBC) cell line (MDA-MB-231LUC+) with a modified syngeneic cell line (E0771LUC+), both expressing luciferase. This comparison was made using several methods, SP stimulation and 3D cell culture models, to better reproduce the heterogenous microenvironment of solid tumors observed in vivo. Furthermore, the susceptibility of the syngeneic cell line (E0771LUC+) to NK1R antagonist (Aprepitant) was tested. Our results indicate that E0771LUC+ recapitulates several essential aspects of the allogenic cell line, rendering this syngeneic line ideal to be used on immune-competent animals during in vivo studies. We have also found that both cell lines are susceptible to SP stimulation, and their proliferation is disrupted by NK1R antagonists (Aprepitant). Follow-up in vivo studies are required to verify and refine these findings.