Multipotent, dedifferentiated cancer stem-like cells from brain gliomas
Multipotent, dedifferentiated cancer stem-like cells from brain gliomas
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DOI：
10.1089/scd.2006.15.423
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发表时间：
2006-06-01
影响因子：
4
通讯作者：
Cha, Seung Heun.
中科院分区：
文献类型：
--
作者：
Kang, Soo Kyung;Park, Jong Bae.;Cha, Seung Heun.
在现代癌症生物学中，外部因素和生态位可以作用于分化的组织细胞，通过诱导成熟成体细胞去分化而导致癌症。最近，我们发现胶质瘤癌细胞的去分化改变了成熟和神经干细胞（NSC）相关基因的表达，因为癌细胞通过下调与神经成熟标志物相关的基因和上调作为原始NSC标志物的基因来适应血清剥夺环境和细胞间相互作用。去分化神经胶质瘤癌细胞的神经发生也显示出与神经胶质细胞和少突胶质细胞标记物高度减少相关的神经元标记物高度增加。经过化疗药物治疗后，去分化的癌细胞表现出很强的耐药性，细胞生长持续活跃。移植到严重联合免疫缺陷 (SCID) 小鼠大脑后，去分化的癌症干细胞迁移并持续活跃增殖超过 4 周。我们还进行了微阵列分析，并表征了具有去分化癌症干细胞样细胞的对照癌细胞中的基因表达模式。我们描述了重要增殖信号蛋白、原始神经谱系相关蛋白、癌症基因和转运蛋白基因的具体数量。在本报告中，我们提出脑肿瘤和正常组织的去分化过程可能导致脑癌的恶性和侵袭性。
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.