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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness
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Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness

机译：卵巢癌侧群定义具有干细胞样特征和苗勒抑制物质响应性的细胞

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摘要

The recent identification of "side population" (SP) cells in a number of unrelated human cancers and their normal tissue sources has renewed interest in the hypothesis that cancers may arise from somatic stem/progenitor cells. The high incidence of recurrence attributable to multidrug resistance and the multiple histologic phenotypes indicative of multipotency suggests a stem cell-like etiology of ovarian cancer. Here we identify and characterize SP cells from two distinct genetically engineered mouse ovarian cancer cell lines. Differential efflux of the DNA-binding dye Hoechst 33342 from these cell lines defined a human breast cancer-resistance protein 1-expressing, verapamil-sensitive SP of candidate cancer stem cells. In vivo, mouse SP cells formed measurable tumors sooner than non-SP (NSP) cells when equal numbers were injected into the dorsal fat pad of nude mice. The presence of Mullerian Inhibiting Substance (MIS) signaling pathway transduction molecules in both SP and NSP mouse cells led us to investigate the efficacy of MIS against these populations in comparison with traditional chemotherapies. MIS inhibited the proliferation of both SP and NSP cells, whereas the lipophilic chemotherapeutic agent doxorubicin more significantly inhibited the NSP cells. Finally, we identified breast cancer-resistance protein 1-expressing verapamil-sensitive SPs in three of four human ovarian cancer cell lines and four of six patient primary ascites cells. In the future, individualized therapy must incorporate analysis of the stem cell-like subpopulation of ovarian cancer cells when designing therapeutic strategies for ovarian cancer patients.
机译：最近在许多不相关的人类癌症及其正常组织来源中发现“侧群”（SP）细胞已引起人们对癌症可能源自体干/祖细胞的假设的重新关注。归因于多药耐药性的复发率很高，并且表明多能性的多种组织学表型表明卵巢癌的干细胞样病因。在这里，我们从两种不同的基因工程小鼠卵巢癌细胞系中鉴定和表征SP细胞。 DNA结合染料Hoechst 33342与这些细胞系的差异外排定义了表达人类乳腺癌抗性蛋白1的维拉帕米敏感SP候选癌细胞。在体内，当将裸鼠的背部脂肪垫注射相同数量的小鼠SP细胞时，它们会比非SP（NSP）细胞更快地形成可测量的肿瘤。 SP和NSP小鼠细胞中均存在Mullerian抑制物质（MIS）信号转导通路分子，这使我们能够研究MIS与传统化学疗法相比对这些人群的功效。 MIS抑制SP和NSP细胞的增殖，而亲脂性化疗剂阿霉素更明显地抑制NSP细胞。最后，我们在四个人类卵巢癌细胞系中的三个和六个患者原发性腹水细胞中的四个中鉴定了表达乳腺癌抗性蛋白1的维拉帕米敏感SP。将来，在为卵巢癌患者设计治疗策略时，个性化治疗必须纳入对卵巢癌细胞样干细胞亚群的分析。

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