e11552 Background: Enriched environment (EE) by promoting physical activity and social communication reduces development of tumors such as in colon cancer. It seems to act particularly through a decrease of leptin production which linked to breast cancer risk. Thus, the aim of this study was to investigate the effect of EE on the mammary tumor development and to identify the molecular pathways in relation to adipokines secretion. Methods: 3-week-old female C57BL/6 mice were housed in standard environment (SE) or in EE for 9 weeks. A half of EE and SE mice received either EO771 syngeneic cells injection into the inguinal mammary fat pad (EE and SE tumor) or vehicle (EE and SE control). After 3 weeks, the mice were sacrificed for blood and tumor analysis : expression of leptin, COX-2 (inflammation), Ki-67 (proliferation) and caspase 3 (apoptosis) were determined using immunostaining and western blotting. Plasma adipokines were quantified by immunoassay (ELISA, Luminex). Results: Tumor volume and weight were lower in EE mice vs SE tumor (-29% and -26% respectively). COX-2 and Ki67 expressions were decreased (20% and 40% of positive cells respectively) while caspase-3 levels were increased (450% of positive cells) relative to SE tumor (100%). EE control mice showed a significant increase in adiponectin levels but no change in those of leptin, IL-6, TNF-α, PAI-1, MCP-1 and resistin vs SE control. No significant difference between EE and SE tumor groups were observed for these inflammatory markers. Conclusions: These data showed for the first time that EE housing inhibits mammary tumor growth which results in a marked intratumoral COX-2 under-expression and an increase in the plasma adiponectin/leptin ratio without any change in inflammatory response. So, COX-2 and adipokines seem to be key regulating factors in breast carcinogenesis. [Table: see text]
Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function