(770b) The Influence of Matrix Stiffness on the Behavior of Brain Metastatic Breast Cancer Cells
Hyaluronic acid hydrogels of varying stiffness (0.2 kPa - 4.6 kPa), including the range relevant to the brain environment (0.2 kPa - 1kPa) were prepared by functionalizing hyaluronic acid with methacrylate groups followed by crosslinking with dithiothreitol. Hydrogels were also engineered to promote cell adhesion by conjugation of the RGD peptide. MDA-MB-231 Br brain metastatic human breast cancer cells were used in our studies and were seeded on top of hydrogels. We first studied the dependence of metastatic breast cancer cell adhesion on the hydrogel stiffness and surface concentration of RGD and observed that the breast cancer cell adhesion increased with increasing hydrogel stiffness and RGD concentration. We also observed that the cell morphology was significantly affected by the hydrogel stiffness and cell spreading area increased with increasing hydrogel stiffness and RGD concentration. In addition, we noted that cell proliferation increased with increasing hydrogel stiffness. Our observations, thus far, indicate the activation of mechanotransduction pathways in brain metastatic breast cancer cells. We are currently investigating the role of focal adhesion kinase (FAK) - phosphatidylinositol 3-kinase (PI3K) signaling in stiffness dependent behavior of brain metastatic breast cancer cells. Ultimately, such systems could provide mechanistic insight into the pathways involved in breast cancer brain metastasis enabling development of new therapeutic targets for metastatic disease.