Exploring the role of adipocytes in breast tumor progression (2015)

Undergraduates: Alissa Vanderlinden, James McCann, Lin Xiao Andrew Dudley, Raghu Murthy

Faculty Advisor: Andrew Dudley
Department: Biology

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Among women in the United States, breast cancer is the most commonly diagnosed cancer and the second leading cause of death. During breast tumor progression, the surrounding breast tissue, largely composed of adipose tissue, becomes hardened and fibrotic, promoting inflammation and angiogenesis in tumors. However, the origin of the fibroblasts, major stromal support cells, remains uncertain. My hypothesis to explain the increase in fibrotic tissue and the decrease in adipose tissue is that the adipocytes de-differentiate into fibroblasts. I am also exploring the origin and role of HMGB1, a pro-inflammatory factor highly expressed in adipocytes, in the growth of breast tumors. I have isolated mature adipocytes from mouse mammary fat pads and performed in vitro characterization of these cells. The morphology and adipocyte and fibroblast gene expression are compared before and after co-culture with tumor cells. An in vivo study was also done, in which tumor cells were injected into the mammary fat pads of female mice, half of which were treated with an HMGB1 blocking antibody and half with an igG control. The size of tumors in mammary fat pads of the treated and untreated mice was compared and blood vessels were quantified to observe the possible role of HMGB1. Determining the origin of tumor-associated fibroblasts and identifying tumor promoting factors will offer potential means of cancer therapy by targeting stromal support cells and pro-inflammatory factors.