Department of Urology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Stem Cells Int. 2010 Mar 14;2010:782967. doi: 10.4061/2010/782967.
Side population (SP) cells are an enriched population of stem, and the existence of SP cells has been reported in human cancer cell lines. In this study, we performed an SP analysis using 11 human cancer cell lines and confirmed the presence of SP cells in an embryonic carcinoma cell line, NEC8. NEC8 SP cells showed characteristics of cancer stem cells, such as high growth rate, chemoresistance and high invasiveness. To further characterize the NEC8 SP cells, we used DNA microarrays. Among 38,500 genes, we identified 12 genes that were over-expressed in SP cells and 1 gene that was over-expressed in non-SP cells. Among these 13 genes, we focused on GADD45b. GADD45b was over-expressed in non-SP cells, but the inhibition of GADD45b had no effect on non-SP cells. Paradoxically, the inhibition of GADD45b significantly reduced the viability of NEC8 SP cells. The inhibition of ABCG2, which determines the SP phenotype, had no effect on the invasiveness of NEC8 SP cells, but the inhibition of GADD45b significantly reduced invasiveness. These results suggest that GADD45b, but not ABCG2, might determine the cancer stem cell-like phenotype, such as chemoresistance and the high invasiveness of NEC8 SP cells, and might be a good therapeutic target.
侧群 (SP) 细胞是一种富含干细胞的群体，已经在人类癌细胞系中报道了 SP 细胞的存在。在这项研究中，我们使用 11 个人类癌细胞系进行了 SP 分析，并证实了胚胎癌细胞系 NEC8 中存在 SP 细胞。NEC8 SP 细胞表现出癌症干细胞的特征，例如高增长率、化疗耐药性和高侵袭性。为了进一步表征 NEC8 SP 细胞，我们使用了 DNA 微阵列。在 38500 个基因中，我们鉴定出在 SP 细胞中过表达的 12 个基因和在非 SP 细胞中过表达的 1 个基因。在这 13 个基因中，我们重点关注 GADD45b。GADD45b 在非 SP 细胞中过表达，但 GADD45b 的抑制对非 SP 细胞没有影响。矛盾的是，GADD45b 的抑制显著降低了 NEC8 SP 细胞的活力。决定 SP 表型的 ABCG2 的抑制对 NEC8 SP 细胞的侵袭性没有影响，但 GADD45b 的抑制显著降低了侵袭性。这些结果表明，GADD45b 而不是 ABCG2 可能决定了 NEC8 SP 细胞的癌症干细胞样表型，例如化疗耐药性和高侵袭性，并且可能是一个很好的治疗靶点。
