Artikel
Revisiting the "go or grow" hypothesis in glioma in vivo
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Veröffentlicht: | 9. Juni 2017 |
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Gliederung
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Objective: Glioblastoma is one of the most devastating cancers. Tumor cell infiltration into the surrounding normal brain tissue confounds the limits of standard treatment. It is currently believed that infiltrating tumor cells have low proliferation rates. The “go or grow” hypothesis postulates that migration and proliferation spaciotemporally exclude each other.
Methods: We evaluated the “go or grow” hypothesis using in vivo multiphoton laser scanning microscopy (MPLSM) on S24 primary glioblastoma stem cells (GBMSCs, kept under serum-free, stem-like conditions) in NMRI nude male mice (n = 478 cells in n = 4 mice) with a chronic cranial window. We used a lentiviral-based vector expressing a Tet-Off controlled histone H2B-GFP (Tet-Off-H2B-GFP) reporter gene for the detection of label retaining cells in human glioblastoma.
Results: Our dynamic in vivo microscopy data show that those glioblastoma cells that have migrated away from the tumor bulk significantly express reduced nuclear GFP-staining compared to the tumor cells within the tumor mass. This suggests that GBMSCs with particularly high migration properties also have a history of high proliferation. However, a low number of slow-cycling GBMSCs was detectable at the invasive front. Ongoing experiments investigate how slow-cycling vs. fast-cycling GBMSCs contribute to other aspects of glioma progression, e.g. participation in the tumor microtube-connected glioma network.
Conclusion: In summary, the Tet-Off-H2B-GFP lentiviral reporter represents a convenient and elegant system to study cumulative tumor cell proliferation in relation to other important features of tumor biology. First results using S24 primary glioblastoma stem cells suggest that the “go or grow” hypothesis might have to be revisited.