GFP Reporter Cell Line - LN-229

Glioblastoma multiforme (GBM) is a deadly malignant tumor characterized by the diffuse invasion of tumor cells into the surrounding brain parenchyma. However, the diffusion characteristics of GBM and its relationship with the tumor microenvironment (TME) remain unclear. Here, researchers investigated the interaction between GBM and its surrounding microenvironment using two human glioma cell lines, U87 and LN229, in an orthotopic xenograft animal model. GBM cells exhibited different characteristics in terms of cell growth rate during development, diffusion characteristics of glioma cells along blood vessels, and invasion of the brain parenchyma. Their results suggest that these differences between the two models are partly attributed to differences in the expression of CXCR4 and STAT3, both of which play important roles in tumor progression. Furthermore, GBM showed a large aggregation of intrinsic microglia and peripheral macrophages, but its polarization toward tumor-supporting cells differed. These results indicate that intrinsic factors of GBM and its interaction with the TME determine the diffusion characteristics and potential reactivity of non-cancerous cells within the TME.

Perivascular growth is the most common feature of glioblastoma (GBM), resulting from the migration and distribution of GBM cells near endothelial cells. Brain tissue is divided into 1 to 4 regions from the tumor inoculation site to the ventral surface of the brain: intratumoral region (region 1), tumor-associated boundary (region 2), and distal regions (regions 3 and 4) (Figure 1A). HE staining showed that U87/GFP cells had a clear boundary between regions 2 and 3, while the boundary of LN229/GFP cells was more diffuse. To determine whether the clear boundary of U87/GFP cells and the diffuse distribution of LN229/GFP cells were due to their intrinsic tropism towards blood vessels, researchers stained brain tissue sections from U87/GFP and LN229/GFP xenografts with a specific antibody against the endothelial cell marker CD-31. U87/GFP cells coexisted with blood vessels in regions 1 and 2, but were rare in regions 3 and 4. Clearly, U87/GFP cells were closely associated with CD-31-positive blood vessels in region 3. In contrast, LN229/GFP cells were not only visible in regions 1 and 2, but also abundant in regions 3 and 4 (Figure 1B and C). LN229/GFP cells were found to be associated with blood vessels in all regions (indicated by arrows in Figure 1D). These results suggest that LN229 cells grow at a lower rate than U87 cells, but their infiltration and diffusion are more extensive.

Figure 1. Distinct distribution of GBM around the tumor center. (Han J, et al., 2020)