Contributed Talk

Microenvironmental mechanics contribute to glioblastoma cell behaviour.

Katarzyna Pogoda¹, Paul Janmey²

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Glioblastomas (GBM) are diffuse and highly invasive tumors that originate in brain and make up about 50% of all primary brain and CNS tumors. Unlike solid tumors glioblastomas are characterized by high intratumor heterogeneity and consist of regions with multiple subpopulations of the cells with various extracellular matrix compositions that support development of resistance to radiation and chemotherapy. GBM possess unique soft matter properties, which discriminate them from other soft tissue-derived tumors with relatively low content of fibrous proteins even in high grade tumors. Moreover, the boundary between tumor and normal tissue is not sharp, and single glioma cells rapidly infiltrate different brain regions and proliferate, which leads to recurrence after surgical resection of the primary tumor [1]. For this reason, one of the central therapeutic goals is to limit cell migration and division, and thereby identify molecular regulators of GBM cell motility and proliferation in vitro and in vivo.
Although glioblastoma development is not accompanied by increased stiffening of tumor stroma, as is observed for breast or liver cancer, single glioma cells increase in proliferation, motility and invasiveness when cultured on a soft environment [2]. Hyaluronic acid – the main glycosaminoglycan that occupies a large volume of brain ECM - can form highly hydrated matrices that mimic the stiffness and composition of brain and glioblastoma ECM if supplemented with adhesive ligands like collagen I and laminin. These matrices can be used as a cell culture platform. Single glioblastoma cells respond to the presence of crosslinked hyaluronan of stiffness comparable to human brain by changing their morphology, motility, proliferation and secretory properties similarly as they respond to substrate stiffening reported for cells grown on polyacrylamide hydrogels with different rigidities. This outcome suggests that hyaluronic acid can trigger the same cellular response as can be obtained by mechanical force transduced from a stiff environment and is a first evidence that chemical and mechanical features can induce equivalent structural reaction in cells [3].