Oxytocin administration, but not social housing condition, reduces growth rate of human breast cancer xenografts (MCF7) in SCID mice.

Abstract

Abstract Abstract #5076 Background: Oxytocin decreases human breast cancer cell proliferation in vitro and oxytocin receptors are reported to be present on at least 80% of human breast tumors. Animal studies show increased oxytocin levels in association with pair bonding, maternal care giving and mating behavior. Our experiment tested two hypotheses: 1) exogenous administration of oxytocin(OT) and 2) sibling-group housing, compared to individual housing, will reduce the growth in human breast cancer cell -MCF7-xenografts in SCID mice. We also hypothesized this effect would be mediated by differences in circulating OT. Materials and Methods: A 2 X 2 design was used to study 48 animals. Half of the animals lived in group(GRP) housing, the others were housed singly(SGL). Half of the animals in each housing group received OT (10-9 M) administered by a continuous release pellet(Innovative Research of America) and the others received a placebo(PBO) pellet. At weaning(4 wks), SCID mice were randomized to individual cages vs. groups of 4 mice per cage. At maturation (vaginal cornification-8 wks), continuous release estrogen pellets were implanted and two days later MCF7 cells(0.1ml/10X106)were implanted in the mammary fat pad. Pellets containing OT or PBO were implanted, subcutaneously, 2 days after the MCF7 cells. Plasma was collected 2 days prior to and 2 days following pellet & cell implantation, 14 days later and at sacrifice (41 – 60 d) for analysis of OT concentration using enzyme immunoassay (Assay Designs, Inc). Tumor volumes were measured every three days. Statistical Analyses: A natural log transformation of the plasma OT levels was used to reduce skewness in the observed values. Tumor volumes were converted to cubed root to linearize and a regression line was fit to generate tumor growth rate(slope). Differences in tumor growth rate by housing condition (GRP/SGL), oxy Rx(Y/N) and OT plasma levels were tested by mixed effects ANOVA. Results: OT plasma levels in animals with OT pellets, as compared to PBO, were significantly different at 2 & 14 days after pellet implantation(p=0.001), but not at baseline or at sacrifice. OT plasma levels were higher in group vs single housing (p=.023). Due to the lack of difference in plasma OT at the time of sacrifice, we limited prediction of tumor growth rate to the first 29 days when OT pellets were secreting OT (extrapolation from levels at 2 & 14 days). Slower tumor growth rate occurred with OT treatment compared to PBO(p=0.031), and with higher OT plasma levels(p=0.032) but not with group vs. single housing.
 Discussion: Continuous oxytocin administration over 29 days produced increased oxytocin plasma levels and both were associated with reduced MCF7 xenograft growth rate in SCID mice. Our next step will be to test whether breast tumor oxytocin receptor density moderates the association between plasma oxytocin and tumor growth rate. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5076.