@article {19289, title = {Extracellular matrix inspired models for gastric cancer development: focus on hyaluronan-CD44 interactions}, journal = {Forecast Workshop}, year = {2017}, month = {2017-11-15 00:00:00}, address = {Porto, Portugal}, abstract = {

Glycosaminoglycans (GAGs) are key components of the extracellular matrix (ECM). Among different GAGs, the expression of hyaluronic acid (HA), composed of repeating disaccharides of N-acetyl-glucosamine and glucuronic acid, is a hallmark of different cancers. (1) An impairment in the processes of HA metabolism in cancerous tissues leads to its accumulation: high concentration of HA is typically associated with cancer aggressiveness. (2) On the other hand, HA is one of the main ligands of the cell surface receptor CD44, usually overexpressed by gastric cancer cells. (3) CD44 in cancer cells interacts with HA-rich microenvironments, triggering cell signaling pathways associated with the ability of malignant cells to migrate and invade basement membranes {\textfractionsolidus} ECM, thus leading to formation of metastasis. (4) Herein, we developed a model in which HA with different molecular weights (Mw) is presented in ECM fashion: embedded into highly hydrated interpenetration network. In this model, HA has restricted mobility but it is yet able to reorganize and bind specifically to other biomolecules e.g. its main cell surface receptor CD44. We therefore studied the interactions of these substrates with the gastric cancer cell line MKN45, known to overexpress CD44. We observed that the Mw of HA affects tremendously the cellular response: more cells adhered to substrates with low Mw. However, the formation of invadopodia and the expression of its marker cortactin increased for substrates with higher Mw, i.e. 6.4kDa\<\<752kDa\<1500kDa. Our results indicate that the developed ECM-mimics are feasible tools in the elucidation of GAG-triggered cellular mechanisms associated with cancer development and aggressiveness.

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}, keywords = {CD44, ecm, Hyaluronic acid}, author = {Amorim, S. and Soares da Costa, D. and Freitas, D. and Reis, C. A. and Reis, R. L. and Pashkuleva, I. and Pires, R. A.} }