Multipotent, Dedifferentiated Cancer Stem-like Cells from Brain Gliomas

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Abstract
In modern cancer biology, external factors and niches can act on differentiated tissue cells to cause cancer by inducing dedifferentiation of mature adult cells. Recently, we discovered that dedifferentiation of glioma cancer cells alters the expression of mature and neural stem cell (NSC)-related genes, in that cancer cells adjust to the serum-deprived environment and cell-to-cell interaction by down-regulating genes associated with neural mature markers and up-regulating genes that are primitive NSC markers. Neurogenesis of dedifferentiated glioma cancer cells also showed a highly increased neuronal marker associated with highly decreased glial and oligodendrocyte cell markers. After treatment with chemotherapeutic drugs, dedifferentiated cancer cells showed strong drug resistance and continued active cell growth. After grafting to severe combined immunodeficient (SCID) mouse brains, dedifferentiated cancer stem cells migrated and continued active proliferation for more than 4 weeks. We also performed microarray analysis and characterized the gene expression patterns in control cancer cells with dedifferentiated cancer stem-like cells. We delineated specific numbers of important proliferation signaling proteins, primitive neural lineage-related proteins, cancer genes, and transporter genes. In this report, we propose that the dedifferentiation process of brain tumor and normal tissue may contribute to the malignancy and aggressiveness of the brain cancer.