Mechanoresponse of glioblastoma cells growing on brain-mimicking ECMs

Glioblastoma multiform is one of the most common and aggressive forms of cancer that originates from brain and is characterized by rapid progression and high mortality rate. Unlike breast and some other cancers where the stroma and the tumor itself is substantially stiffer than the surrounding normal tissue, existing data suggest that gliomas can arise without a gross change in the macroscopic tissue stiffness when measured at low strains without compression . Furthermore, extracellular matrix proteins, like collagens, commonly present in other tissues, are nearly absent in normal adult brain. Instead, a large volume of brain ECM consists of glycosaminoglycans – mainly hyaluronic acid (HA), which become enriched witch fibrous proteins only during pathological processes. In our studies, we test the hypothesis that the mechanical cues transmitted from the brain-mimicking ECMs of different physicochemical properties contribute to cell survival and function. Our data shows that glioblastoma cells can adhere and proliferate on the polyacrylamide gels with different stiffness, but their morphology depends strongly on the actual substrate stiffness and type of the ligand used for coating. Moreover, soft hyaluronic acid rich matrices containing integrin ligands such as laminin or collagen-1 in particular can dramatically change glioblastoma cells' mechanoresponse, suggesting that HA-mediated glioma development can be one of the main players during disease progression.Non UBCUnreviewedAuthor affiliation: Institute of Nuclear Physics, PANPostdoctora