Obesity, Adipocytes and Breast Cancer – Insights from Translational Studies
Abstract
Background: Being overweight is becoming the new normal, and more than half of the adult Swedish population is overweight which poses a risk to public health. Overweight and obese women have both an increased risk and a worse prognosis for breast cancer, compared with women of normal weight. The breast cancer incidence in Sweden is increasing, and about one in nine women will be diagnosed with breast cancer during her lifetime. Adipose tissue is in close proximity to tumor cells in the breast microenvironment, and excess body fat and an altered metabolic state may lead to local and systemic molecular changes favoring tumor progression. The underlying biological mechanisms, however, are still not fully understood. The overall objective of this thesis was to bring new insights into the biological processes linking obesity to breast cancer, both through preclinical experimental studies of the interactions of adipocytes and breast cancer cells, as well as through epidemiological studies of women and their body constitution in relation to breast cancer risk and subsequent clinical outcome. Methods: In Paper I-II, an in vitro model mimicking the microenvironment in normal- and obese-like breast cancer patients was established. Effects of the adipocytes secretome on breast cancer cell morphology, proliferation, and motility were investigated. The adipokine secretome was analyzed by proteome profiler array for putative biological mediators. The phosphorylation patterns of protein…
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