Project Summary
Breast cancer is the most common form of cancer in women and is considered a modern-day epidemic,
especially because of the high degree of heterogeneity. Multiple studies have shown that the tumor
microenvironment contributes to cancer growth and chemoresistance. Cancer-adipocyte interactions have
gained increased attention as the crosstalk between them has been shown to promote tumor proliferation and
increased cancer migration. However, the physiological relevance of previous co-culture methods is
questionable. Several past studies did not use human cells, or differentiate between white and brown
adipocytes, which have different phenotypes. In this proposal we will analyze tumor invasiveness of human
triple negative and luminal A breast cancer cells when co-cultured with human brown and white adipocytes. To
do this, we propose to use a 3D multicellular tumor spheroid system. Tumor spheroids provide a physiological
relevant environment to study cancer biology and drug discovery. Compared to 2D paradigms, research shows
3D models better recapitulate chemoresistance and tumor growth found in human in vivo tumors. In the lab, we
have developed a bioreactor that uses surface vibrations to produce Faraday waves that aggregate cells inside
a liquid chamber. Devices with similar technology have been used to assemble scaffold-free 3D cell constructs
and spheroids in a rapid and scalable way, without the need for additional chemicals or intrusive procedures. In
this grant, we also seek to determine if this technology generates multicellular spheroids with greater cell-cell
adhesion, compared to standard self-assembly. To achieve the scientific and technological goals of this grant,
two specific aims are proposed: The first aim will compare the viability and connectivity of multicellular
spheroids formed with our surface vibration bioreactor versus standard self-assembly spheroids. The second
aim will measure changes in tumor invasiveness and proliferation in tumor spheroids made with human cancer
cells and human adipocytes. We will compare two different types of breast cancer cells: triple negative and
luminal A and two different types of adipocytes: white and brown adipocytes. These combinations will allow us
to investigate the interactions of different cancer phenotypes with specific adipocyte cell types. Overall, the
proposed research will have a major scientific and technological impact by expanding our understanding of
breast cancer-adipocyte interactions and testing a technology that could deliver multicellular spheroids with
improved intracellular connectivity in a scalable manner. This will significantly impact the field of cancer biology
and therapeutics, as cancer-adipocyte associations have been observed in a multitude of tumors, including
prostate, ovarian, and pancreatic cancer.
