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首页> 外文期刊>Cell cycle >Ovarian carcinoma tumor-initiating cells have a mesenchymal phenotype
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Ovarian carcinoma tumor-initiating cells have a mesenchymal phenotype

机译：卵巢癌肿瘤细胞具有间充质表型

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Solid tumors appear to contain a subpopulation of cells (tumor-initiating cells, TICs) that not only drives and sustains tumor growth, but is possibly responsible for recurrence. We isolated, after enzymatic digestion of primary ovarian carcinoma samples, a subpopulation of cells propagating as non-adherent spheres in medium suitable for tumor stem cells. These cells were able to self-renew in vitro, as suggested by PKH-26 staining studies, were tumorigenic and acquired an epithelial morphology when grown in FBS-supplemented medium, losing their tumorigenic potential. Interestingly, the tumorigenic potential of PKH-26 high- and PKH-26 neg-sorted cells was similar. These TIC-enriched cultures showed higher levels of genes involved in stemness than differentiated cells derived from them and were more resistant to the cytotoxic effects of some drugs but equally sensitive to others. The higher level of ABCG2 efflux pump could explain increased resistance to taxol and VP16, and higher levels of genes involved in nucleotide excision repair partially explain the resistance to cisplatin. These cells express mesenchymal markers and epithelial transition could be induced when cultured in differentiating conditions, with a loss of invasive potential. These data suggest that ovarian cancer is a stem cell disease and should help elucidate the role of these cells in the aggressive phenotype of this tumor and find new therapeutic strategies to reduce resistance to current chemotherapeutic drugs.
机译：实体瘤似乎包含细胞亚群（肿瘤引发细胞，TIC），不仅驱动并维持肿瘤的生长，而且可能导致复发。在对原发性卵巢癌样品进行酶消化后，我们在适合于肿瘤干细胞的培养基中分离出了作为非粘附球体繁殖的细胞亚群。如PKH-26染色研究所示，这些细胞能够在体外自我更新，具有致瘤性，并且在补充FBS的培养基中生长时具有上皮形态，丧失了致瘤性。有趣的是，PKH-26高分选细胞和PKH-26 neg分选的细胞的致瘤潜力相似。这些富含TIC的培养物显示出与干细胞有关的基因水平高于衍生自它们的分化细胞，并且对某些药物的细胞毒性作用更具抵抗力，但对其他药物同样敏感。较高水平的ABCG2外排泵可以解释对紫杉醇和VP16的耐药性增加，而参与核苷酸切除修复的基因水平较高可以部分解释对顺铂的耐药性。这些细胞表达间充质标志物，在分化条件下培养时可诱导上皮转化，但侵袭力丧失。这些数据表明，卵巢癌是一种干细胞疾病，应有助于阐明这些细胞在该肿瘤的侵袭性表型中的作用，并找到新的治疗策略以降低对当前化疗药物的抵抗力。

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