Abstract 3173: The NLRC4 inflammasome promotes breast cancer progression in diet-induced obese mice

Obesity is not only a known risk factor for the development of ER+ breast cancer in postmenopausal woman, but is also associated with a poor clinical outcome across all subtypes of breast cancer. Obesity is also one of the only known risk factors for the development of invasive ductal carcinoma (IDC) versus ductal carcinoma in-situ (DCIS; non-invasive). A number of hypotheses have been proposed to explain the association between obesity and breast cancer progression. One such hypothesis is that the chronic inflammation in adipose tissue associated with obesity, especially adipose tissue in the mammary glands, creates a microenvironment that promotes breast cancer progression by acting as a reservoir of pro-inflammatory cytokines (including interleukin IL-1β and IL-6). One source of pro-inflammatory cytokines in adipose tissue is activated inflammasomes in infiltrating macrophages. Inflammasomes are multiprotein complexes whose main function is the activation of IL-1β and IL-18 during inflammation via Caspase 1-mediated proteolytic cleavage. Chronic inflammation, NLRP3 inflammasome activation and IL-1β are thought to be a major cause of obesity-associated insulin resistance and are involved in many human diseases including type-2 diabetes and cancer. However, the mechanism linking obesity and breast cancer progression remains unknown. We hypothesize that obesity-induced inflammasome activation in mammary adipose tissue results in active IL-1β which in turn promotes breast ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Immunology Source Type: research