Tumor microenvironment: What is the role of adipocytes during tumor development? (2014)

Undergraduate: Alissa Vanderlinden

Faculty Advisor: Andrew Dudley
Department: Biology

---

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 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. To track the fate of the adipocytes in vivo during tumor growth, Adipoq-cre mice are crossed with ZS-green reporter mice to produce Zs-greenAdi-cre mice whose mature adipocytes are tagged with the fluorescent protein ZS-green. I have optimized a mammary tumor spheroid model that accurately represents clinical tumor growth for injection into the mammary fat pads of the Zs-greenAdi-cre reporter mice. Tumor-associated adipose tissue will be harvested and the gene expression and morphology will be compared to normal adipose tissue. Determining the origin of tumor-associated fibroblasts will offer potential means of cancer therapy by targeting stromal support cells.