Neuropeptide Y promotes chemotaxis in the 4T1 and MDA‐MB 231 breast cancer cell lines

The effect of the sympathetic neuronally derived neuropeptide Y (NPY) on the progression of breast cancer is gaining research interest. We previously reported that the tumors from a syngenic murine model of breast cancer (4T1 cell line) express sympathetic nerves and NPY receptors (Y1R, Y2R and Y5R). Our current objective was to evaluate the contributions of NPY on breast cancer cell chemotaxis. Using the 4T1 (mouse) and MDA‐MB 231 (human) breast cancer cell lines, we assessed the effect of NPY on cellular chemotaxis, in vitro , using a modified Boyden chamber apparatus. To ascertain specific Y‐receptor contributions to the chemotactic effect of NPY, cells were incubated with antagonists for Y1 (BIBP 3226), Y2 (BIIE 0246) and Y5 (L‐152,804) receptors in the presence of NPY. NPY produced potent and concentration‐dependent increases in chemotaxis with a peak effective concentration of 10 −8 M and 10 −7 M in 4T1 (r 2 =0.97) and MDA‐MB 231 (r 2 =0.97) cells, respectively. As well, Y2R and Y5R blockades independently attenuated this response (p<0.01) in a concentration‐dependent manner (r 2 =0.98). These data illustrate that NPY promotes chemotaxis in the 4T1 and MDA‐MB 231 cell lines through activation of Y2 and Y5 receptors. NSERC.