Multilayer Platform to Model the Bioactivity of Hyaluronic Acid in Gastric Cancer

Hyaluronic acid (HA) has a key role in cancer progression. The HA’s molecular weight (Mw) is altered

in this pathological state: increased concentration of shorter fragments due to the overexpressed

hyaluronidases and ROS. Aiming to mimic this microenvironment, we developed a Layer-by-Layer

(LbL) platform presenting HA of different Mws, namely 6.4, 752 and 1500kDa, to study the influence of

HA Mw on the formation of focal adhesion sites (FAs), and the involvement of paxillin and CD44 in this

process. High paxillin expression and formation of FAs, via CD44, is observed for MKN45 cells seeded

on LbLs presenting HA 6.4kDa, with the activation of the ERK1/2 pathway, responsible for cell motility

and tumour progression. In contrast, activation of p38 pathway, usually related with cancer latency, is

observed for cells seeded on LbLs with high Mw HA, i.e. 1500kDa. Overall, we demonstrate the

suitability of the developed platform to study cancer invasiveness.