Assessment of brain tumor cell motility in vivo and in vitro

Abstract

Brain tumor dispersal far from bulk tumor contributes to and, in some instances, dominates disease progression. Three methods were used to characterize brain tumor cell motility in vivo and in vitro: 1) 2 weeks after implantation in rat cerebral cortex, single C6 cells labeled with a fluorescent tag had migrated to brain sites greater than 16 mm distant from bulk tumor; 2) time-lapse videomicroscopy of human brain tumor cells revealed motility of 12.5 microns/hr. Ruffling leading edges and pseudopod formation were most elaborate in more malignant cells; 3) an in vitro assay was devised to quantitatively evaluate motility from a region of high cell density to one of lower cell density. Human brain tumor cells were plated in the center of a petri dish, washed, and refed, establishing a 2-cm circular zone of cells in the dish center. Motility was determined by counting cells daily at predetermined distances from the central zone perimeter. Cells were found 1 cm from the perimeter by 24 hours and 3 cm from the perimeter by 4 days. Increasing serum concentration increased motility; however, neither fibronectin nor arrest of cells in the G0 phase by hydroxyurea altered motility. The addition of cytochalasin B to block cytoskeletal assembly prevented cell motility. Motility increased with increased malignancy. Subpopulations of cells were created by clonal amplification of cells that had migrated most rapidly to the dish periphery. Although morphologically indistinguishable when compared to the original cell line from which they were derived, these subpopulations demonstrated significantly increased motility.

Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases

“…Infiltrative glioma cells are a particular therapeutic challenge owing to their diffuse localization, distance from the initial site of resection, protection by an intact blood-brain barrier (Kenney et al, 1992) and low frequency of mitosis (Chicoine and Silbergeld, 1995). The targeting of these invasive glioma cells remains elusive because of a deficiency in our understanding of the molecular events underlying tumor invasion.…”

Reduced Expression of the Hyaluronan and Proteoglycan Link Proteins in Malignant Gliomas

“…We used a radial-dispersion model in which a cell aggregate is plated on a precoated surface and acts as a "tumor bulk" from where cells detach and migrate radially (Fig. 4A) (24). Cell migration in this model is a result of cell-substrate versus cell-cell adhesive forces, mimicking the detachment and invasive properties of malignant brain tumor cells (33).…”

Modelling biological invasions: Individual to population scales at interfaces

“…Hence, an extensive literature has developed with the purpose of assessing the spread of malignant glial cells given clinical imaging data (Swanson et al, 2002a(Swanson et al, , 2002bHatzikirou et al, 2005;Ellingson et al, 2011;Konukoglu et al, 2010a;Kim et al, 2009;Bearer et al, 2009;Eikenberry et al, 2009), utilising modelling frameworks that exploit the fact that these cells are highly motile and dispersive, which has been observed and even quantified in vitro and in vivo (Chicoine and Silbergeld, 1995). Quantitative comparisons with Fickian diffusion have also exhibited favourable agreement for malignant glial cells within a collagen gel, on supplementing the theoretical model with cell proliferation and a distinction between the glioma core and its invasive rim, which allows for cell shedding dynamics (Stein et al, 2007).…”