Functional surfaces for high-resolution analysis of cancer cell interactions on exogenous hyaluronic acid

Hyaluronic acid, a nonsulfated, linear glycosaminoglycan, is ubiquitously distributed in the extracellular matrix and is known to facilitate tumor progression by enhancing invasion, growth, and angiogenesis. Native HA has been attached to substrates to create patterned surfaces resistant to cell adhesion, and has been utilized in a variety of cell adhesion studies using either non covalently bound layers patterned by soft lithography or related methods. We use a new approach to study cell interactions with HA-presenting regions, by covalently linking HA adjacent to PEG-ylated regions, which resist cell adhesion. Colon and breast cancer cells seeded on the patterned HA surfaces adhere preferentially on HA-presenting regions and proliferate there. Furthermore, we demonstrate that cell adhesion is inhibited with the blocking of HA receptor, CD44, and that cellular adhesive processes, through protrusions spreading onto the HA surface, enhance spreading and movement outside the HA-presenting regions. Overall, this approach allows high-resolution analysis of cancer cell attachment, growth, and migration on exogenous native HA.