Professor Chun Liu currently is an associate professor of First Affiliate Hospital of Sun Yat-sen University. Her major research interest focuses on the development of biomaterials and 3D models of tumor microenvironment. She graduated from Michigan State University in 2015, with a Ph.D. degree in Chemical engineering. After graduation, she worked as an research fellow in the Department of Radiology at University of Michigan. She came back China and started my current position since 2019. She has published more than 40 research articles including Nature Communications, Cell Reports Medicine, Acta Biomaterialia, Advanced Healthcare Materials., Tissue Engineering & Regenerative Medicine, Tissue Engineering, Journal of Applied Polymer Science. She also had 1 US patent and 1 Chinese patent authorized.

Topic title: Heterogeneous microenvironmental stiffness regulates pro-metastatic functions of breast cancer cells

Abstract:

Besides molecular and phenotypic variations observed in cancer cells, intratumoral heterogeneity also occurs in the tumor microenvironment. Correlative stiffness maps of different intratumor locations in breast tumor biopsies show that stiffness increases from core to periphery. However, how different local ECM stiffnesses regulate key functions of cancer cells in tumor progression remains unclear. Although increased tissue stiffness is an established driver of breast cancer progression, conclusions from 2D cultures do not correspond with newer data from cancer cells in 3D environments. Many past studies of breast cancer in 3D culture fail to recapitulate the stiffness of a real breast tumor or the various local stiffnesses present in a tumor microenvironment. In this study, we developed a series of collagen/alginate hybrid hydrogels with adjustable stiffness to match the core, middle, and peripheral zones of a breast tumor. We used this hydrogel system to investigate effects of different local stiffness on morphology, proliferation, and migration of breast cancer cells. RNA sequencing revealed critical cellular processes regulated by tissue mechanics, including metabolism and angiogenesis. We discovered that tumor cells in soft environment enriched YAP1 and AP1 signaling related genes, whereas tumor cells in stiff envrionment became more pro-angiogenesis by upregulating fibronectin 1 (FN1) and matrix metalloproteinase 9 (MMP9) expression. This systematic study defines how the range of environmental stiffnesses present in a breast tumor regulates cancer cells, providing new insights into tumorigenesis and disease progression, at the tumor-stroma interface.