Hyaluronic acid of low molecular weight triggers the invasive “hummingbird” phenotype on gastric cancer cells

Abstract

The overproduction and deposition of hyaluronic acid (HA) of different sizes in the tumor microenvironment is associated with cancer metastasis. Here, the development of layerâ byâ layer (LbL) constructs containing HA of different molecular weights (i.e., 5.6, 618, and 1450Â kDa) that mimic the HAâ rich cancer extracellular matrix is described to study the effect of the HA's size on the behavior of gastric cancer cells (AGS). The results demonstrate that LbL constructs with short HA, i.e., 5.6Â kDa, activate the cytoskeleton rearrangement leading to the â hummingbirdâ morphology, promote high cellular motility, and activate signaling pathways with increased expression of pâ ERK1/2 and pâ AKT. In addition, it is demonstrated that this malignant transformation involves an active participation of the HA coreceptor RHAMM in AGS cells.