A Tumor-derived Niche Cell Promotes Tumor Growth in Medulloblastoma
Ventura, Patrick, Microbiology - Graduate School of Arts and Sciences, University of Virginia
Zong, Hui, Department of Microbiology, University of Virginia
Niche cells play critical roles in tumor initiation, progression, and metastasis. However, our understanding of niche establishment and function has been hampered by the complex cell composition in the tumor mass. Here we used a mouse genetic system called Mosaic Analysis with Double Markers (MADM) to analyze the tumor niche in medulloblastoma, taking advantage of the unequivocal GFP-labeling of tumor cells by the system. While tumor-infiltrating blood vessels and immune cells are free of GFP-labeling, surprisingly, astrocytes within tumors are all GFP-positive, suggesting that they are derived from tumor cells. Subsequent analysis confirmed the relationship between tumor cells and niche astrocytes in human medulloblastoma. Finally, tumor-derived astrocytes can support tumor cell survival and proliferation in vitro and coincide with tumor progression in vivo. In summary, our findings revealed a self-building niche in medulloblastoma, in which some tumor cells transdifferentiate into niche astrocytes that in turn support tumor growth.
PHD (Doctor of Philosophy)
medulloblastoma, transdifferentiation, astrocyte, niche, microenvironment, genetic mosaic
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