Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Br J Cancer. 2011 Apr 26;104(9):1410-7. doi: 10.1038/bjc.2011.94. Epub 2011 Apr 5.
The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a small subpopulation of cells, which have indefinite proliferation and differentiation potentials and give rise to phenotypically diverse cancer cells. Cancer stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the 'side population' (SP).
The Hoechst efflux assay was used to isolate and characterize the SP from murine D121 lung carcinoma cells. Here, we demonstrated that D121-SP cells contain cancer stem cell characteristics, that is, upregulation of the transcription factors SOX2 and Oct 4 in D121-SP cells. In addition, the migration of D121-SP was decreased, and apoptosis of D121-SP was upregulated following knocking down of SOX2 in D121 cells. Importantly, downregulation of SOX2 in D121 cells markedly suppressed their metastatic potential in syngeneic mice.
These results suggest that the SP is an enriched source of lung tumour cells with stem cell properties and that SOX2 has an important role in maintaining stem cell properties and functions that may be a potential target for effective lung cancer therapy.
癌症干细胞假说认为，肿瘤克隆仅由一小部分具有无限增殖和分化潜能的细胞维持，这些细胞产生表型多样的癌细胞。癌症干细胞可以通过排出 Hoechst 33342 染料的能力来分离，被称为“侧群”（SP）。
采用 Hoechst 排岀实验从小鼠 D121 肺癌细胞中分离和鉴定 SP。在此，我们证明 D121-SP 细胞具有癌症干细胞的特征，即 D121-SP 细胞中转录因子 SOX2 和 Oct4 的上调。此外，D121 细胞中 SOX2 的敲低可降低 D121-SP 的迁移能力，并上调 D121-SP 的凋亡。重要的是，D121 细胞中 SOX2 的下调显著抑制了它们在同基因小鼠中的转移潜能。
这些结果表明，SP 是富含具有干细胞特性的肺肿瘤细胞的来源，SOX2 在维持干细胞特性和功能方面起着重要作用，可能成为有效肺癌治疗的潜在靶点。
