Obesity is becoming a global epidemic, leading to increased rates of multiple types of cancer including breast, kidney, colorectal, pancreatic, and esophageal.  One of the important risk factors associated with breast cancer in postmenopausal women is obesity.  However, regardless of menopausal status, obese women that are diagnosed with breast cancer develop larger, more aggressive tumors, with an increased incidence of metastases. Since breast tissue is a reservoir of subcutaneous adipose tissue,elucidating the changes in adipose tissue under conditions of obesity is critical for prevention and treatment of obesity-associated cancer.   In order to understand how obesity alters the microenvironment of the breast, we utilize high fat diet and transgenic mouse models of obesity, a novel human xenograft model to observe tumor development, and complementary in vitro cell culture models. Our lab has three main focus areas:

1. How do adipokines secreted by obese adipose tissue contribute to breast tumorigenesis? Adipose tissue is a major endocrine organ, secreting adipokines which act locally and systemically.  Multiple adipokines have been implicated in the pathogenesis of breast cancer, including insulin-like growth factor-1 (IGF-1) and leptin. To examine how these adipokines act within the microenvironment of the breast, we isolate specific cell types, such as adipocytes, adipose stem cells and macrophages, to study in vitro, as well as for use in a novel xenograft model to identify local microenvironmental effects.  These findings then can be applied to the more complexenvironment of obesity utilizing a high fat diet model of obesity as well as transgenic mice.  These studies may uncover signaling interactions that can be targeted therapeutically in obese women with breast cancer.
2. How do stromal cells in the obese microenvironment contribute to the pathogenesis in breast cancer?  Multiple different stromal cell types reside in adipose tissue, including adipocytes, immune cells, endothelial cells, and multipotent adiposestem cells.  Under normal conditions these cell interact to regulate angiogenesis and adipogenesis.  However, under conditions of obesity, adipose depots become sites of chronic inflammation, with a recruitment of macrophages, increased tissue fibrosis, and abnormal blood vessel formation.  Both immune cells as well as adipocytes have been shown to secrete cytokines which have been implicated in tumor promotion. Understanding how obesity impacts the interactions among stromal cells with each other and with epithelial cells within the normal breast is critical for understanding how they contribute to tumor growth in the microenvironment of the developing tumor.
3. Why does menopause alter the risk for obesity in breast cancer? Obesity significantly increases the risk of breast cancer in postmenopausal women, but paradoxically, reduces the risk in young women.  The reasons underlying this difference in risk are not clear.  Development of the breast is critically dependent upon ovarian hormones, and estrogen levels have been shown to impact breast cancer risk. Following menopause, estrogen is synthesized locally by aromatase activity in obese adipocytes.  In young women, obesity may also significantly alter ovarian function. Understanding the relationship between obesity and estrogen may be critical for unraveling the risk for breast cancer in postmenopausal women.