The tumour microenvironment is a complex niche of proteins, glycoproteins, glycosaminoglycans and different cell types. The glycosaminoglycan Hyaluronic Acid (HA) is one of the major constituents of the extracellular matrix (ECM) and its’ molecular weight (Mw) is linked to cancer cells behaviour, i.e. low Mws are associated to migration, whereas the high Mw HA have been linked to cellular latency and apoptosis. [1-3] In addition, it has been reported that the cancer invasive character is promoted by the crosstalk between cancer cells and mesenchymal stem cells (MSCs). In fact, MSCs induce Epithelial to Mesenchymal Transition (EMT) on cancer cells. In EMT cancer cells lose their polarity and intercellular junctions, with an upregulation of mesenchymal markers acquiring an enhanced migration character. [3,4] Herein, we developed a 3D co-culture model that recapitulates the tumour microenvironment. This model is based on a core-shell hydrogel, where the core can be tuned to present HA of specific Mws. We used this system to study the impact of HA Mw and the presence of MSCs in gastric cancer invasiveness. This was achieved using co-cultures of MKN45 cancer cells encapsulated in the core of the 3D system (alginate presenting HA of 6.4, 752 or 1500kDa) and bone marrow MSCs in the alginate-only shell. Under these experimental conditions we found a correlation between the HA’s Mw and cancer invasiveness: migration of MKN45 is promoted by short HA (6.4 kDa). In addition, the presence of MSCs promote EMT on MKN45 cancer cells, which was confirmed by the overexpression of the mesenchymal markers vimentin and n-cadherin. Furthermore, no EMT was detected on cancer cells cultured in the presence of MSCs conditioned media, showing that the MSCs-MKN45 crosstalk is necessary to promote the EMT on the MKN45 cancer cells. Our data clearly demonstrate that: 1) the size of HA Mw influences cancer cells migration and invasiveness, and 2) the EMT occurs in dependence of HA Mws’ and the physical crosstalk between MSCs and cancer cells.

3D co-culture model that mimic the role of hyaluronic acid on gastric cancer invasiveness

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.