Obesity has been linked to an elevated risk for postmenopausal breast cancer, presumably due to increased production of estrogen by adipocytes. We hypothesize that the obese state may also regulate circulating levels of other hormones, growth factors, and cytokines (eg, insulin, IGF-I, leptin), which may also play a role in mammary tumorigenesis. To address this hypothesis, blood was collected from obese and lean rats genetically disposed to be obesity prone or obesity resistant. Three types of hormone-unresponsive mammary cell lines, one non-transformed and two transformed, were used in functional in vitro assays designed to assess the differential effects of sera and/or plasma from obese and lean rats on cell proliferation, motility, and invasiveness. Results revealed that sera or plasma from obese rats increased cell proliferation compared to sera or plasma from lean rats. Obese sera/plasma also increased tumor cell motility and invasiveness in trans-well filter assays. These findings suggest that the obese state alters circulating factors, which foster increased proliferative, motile, and invasive activity in mammary epithelial cells and mammary tumor cells compared to the lean state.
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