The proliferative effects of sympathetic nerves and neuropeptide Y in a 4T1 cell breast cancer model

Abstract

The functional impact of sympathetically released neuropeptide Y (NPY) on breast cancer has been a question of growing interest due to the expression of NPY receptors in several cancer cell lines. Recently, our group reported that the 4T1 cell line expresses NPY receptors (Y1 &Y2) and mammary tumors grown from this cell line are sympathetically innervated. In the current study we evaluated the effect of NPY on 4T1 cell proliferation using 96‐hr treatment with NPY (10−12 to 10−6M) and observed an increase in proliferation (MTS‐based assay) in treated cells compared to controls (10−8: 55%, 10−7:122%, 10−6: 157%, P < 0.05). Additionally, we examined the effect of chemical sympathectomy (via 6‐hydroxydopamine bromide, 6OHDA) on in vivo tumor growth. 4T1 cells (105)were injected into the sympathectomized inguinal mammary fat pad (200 μg 6OHDA × 2 localized injections, 1 week prior to 4T1 inoculation) and intact fat pad of female BALB/c mice (n = 5/group). Tumor growth was monitored by caliper measures over 21 days and animals were sacrificed and tumors were harvested and weighed. Tumor volume was lower in sympathectomized animals compared to intact animals at all time points (wk1: 70%, wk2: 44% & wk3: 45%, P < 0.05), and final tumor mass was 52% of intact tumors (P < 0.05). These findings suggest that NPY and sympathetic nerves impact cellular proliferation in this model. NSERC & Canadian Breast Cancer Foundation.