Identification and expansion of the tumorigenic lung cancer stem cell population
Identification and expansion of the tumorigenic lung cancer stem cell population
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DOI：
10.1038/sj.cdd.4402283
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发表时间：
2008-03-01
影响因子：
12.4
通讯作者：
De Maria, R.
中科院分区：
文献类型：
--
作者：
Eramo, A.;Lotti, F.;De Maria, R.
肺癌通常无法治愈，并且仍然是男性和女性的主要癌症杀手。最近的证据表明，肿瘤含有一小群负责肿瘤维持和扩散的癌症干细胞。识别维持肺癌的致瘤人群可能对有效治疗的发展有重要贡献。在这里，我们发现，在小细胞和非小细胞肺癌的致瘤细胞是一种罕见的未分化细胞表达CD133，抗原存在于细胞膜的正常和癌原细胞的造血，神经，内皮和上皮谱系。肺癌CD 133（+）细胞能够在含有表皮生长因子和碱性成纤维细胞生长因子的无血清培养基中作为肿瘤球无限生长。在免疫功能低下的小鼠中注射10 4个肺癌CD 133（+）细胞，很容易产生与原始肿瘤表型相同的肿瘤异种移植物。分化后，肺癌CD 133（+）细胞获得了特异性谱系标志物，同时失去了致瘤潜力和CD 133表达。因此，肺癌含有一种罕见的CD133（+）癌症干细胞样细胞群体，能够自我更新并产生无限的非致瘤细胞后代。这种致瘤性人群的分子和功能表征可能提供有价值的信息，以在临床环境中加以利用。
Lung carcinoma is often incurable and remains the leading cancer killer in both men and women. Recent evidence indicates that tumors contain a small population of cancer stem cells that are responsible for tumor maintenance and spreading. The identification of the tumorigenic population that sustains lung cancer may contribute significantly to the development of effective therapies. Here, we found that the tumorigenic cells in small cell and non-small cell lung cancer are a rare population of undifferentiated cells expressing CD133, an antigen present in the cell membrane of normal and cancer-primitive cells of the hematopoietic, neural, endothelial and epithelial lineages. Lung cancer CD133(+) cells were able to grow indefinitely as tumor spheres in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. The injection of 10 4 lung cancer CD133(+) cells in immunocompromised mice readily generated tumor xenografts phenotypically identical to the original tumor. Upon differentiation, lung cancer CD133(+) cells acquired the specific lineage markers, while loosing the tumorigenic potential together with CD133 expression. Thus, lung cancer contains a rare population of CD133(+) cancer stem-like cells able to self-renew and generates an unlimited progeny of non-tumorigenic cells. Molecular and functional characterization of such a tumorigenic population may provide valuable information to be exploited in the clinical setting.