Three-dimensional constructs using hyaluronan cell carrier as a tool for the study of cancer stem cells.
BACKGROUND
Cancer research focuses increasingly on cancer stem cell study as those cells are thought to be the root of chemo and radioresistance of the most aggressive cancer types. Nevertheless, two-dimensional (2D) cell culture and even three-dimensional (3D) spheroid models, with their limited ability to reflect cell-extracellular matrix interactions, are not ideal for the study of cancer stem cells (CSCs). In this study, we establish a 3D in vitro cancer model using a synthetic and natural scaffold with tunable features and show that U87 cells cultured in this system acquire a stem-cell like phenotype.


METHODS
U87 astrocytoma cells were grown on polycaprolactone (PCL)-2D flat substrates (2D) and PCL-3D scaffolds (3D) eventually containing hyaluronic acid (3D-HA). Cell viability, growth patterns, morphology, and cell surface marker expression (CD44, RHAMM and CD133) were studied to assess the effect of 3D culture and presence of HA.


RESULTS
3D scaffold, but most prominently presence of HA induced changes in cell morphology and marker expression; 3D-HA cultures showed features of aggregates; moreover, markedly increased expression of Nestin, CD44, RHAMM, and CD133 in 3D-HA scaffolds were found.


CONCLUSIONS
the behavior of U87 in our 3D-HA model is more similar to tumor growth in vivo and a stem-like phenotype is promoted. Thus, the 3D-HA scaffold could provide a useful model for CSCs study and anti-cancer therapeutics research in vitro and may have preclinical application for the screening of drug candidates.
['Martínez-Ramos|Cristina|C|', 'Lebourg|Myriam|M|']
D001254:Astrocytoma D018914:Cells, Immobilized D015972:Gene Expression Regulation, Neoplastic D006801:Humans D006820:Hyaluronic Acid D009363:Neoplasm Proteins D014411:Neoplastic Stem Cells D018874:Spheroids, Cellular
cancer stem cells 3D scaffold hyaluronic acid/hyaluronan hydrogel tumor model