CD44+/CD24-ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival

CD44+/CD24-ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival
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DOI:
10.1007/s10585-012-9482-4
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发表时间:
2012-12-01
影响因子:
4
通讯作者:
Rocconi, Rodney P.
Rocconi, Rodney P.
中科院分区:
医学3区
文献类型:
--
作者:
Meng, Erhong;Long, Beverely;Rocconi, Rodney P.

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具有表面标记CD44+/CD24-的癌细胞先前被描述为具有癌症干细胞样特性。本文评价了卵巢癌细胞系的这些特性。CD44+/CD24-细胞的比例对应于卵巢癌细胞系组织学亚型的临床侵袭性。与其他表型相比,CD44+/CD24-细胞表现出增强的渐进式分化,并且在SKOV3和OV90细胞系中显示出60倍的Matrigel侵袭(p均< 0.001)。CD44+/CD24-显示出对所有细胞系中使用的所有化疗药物的显著耐药性,与基线相比,耐药性增加了71- 93%。以腹水中发现的25% CD44+/CD24-卵巢癌细胞为阈值,患有> 25% CD44+/CD24-的患者更容易复发(83% vs. 14%, p = 0.003),中位无进展生存期更短(6个月vs. 18个月,p = 0.01)。总之,卵巢癌细胞的CD44+/CD24-表型显示出癌症干细胞样的特性,增强了分化、侵袭和对化疗的抵抗。这种CD44+/CD24-表型与卵巢癌患者复发风险增加和无进展生存期缩短的临床终点相关。
Cancer cells with the surface marker profile CD44+/CD24- have previously been described to possess cancer stem cell-like properties. This manuscript evaluates those properties in ovarian cancer cell lines. The proportion of CD44+/CD24- cells corresponded to the clinical aggressiveness of each ovarian cancer cell line histologic subtype. CD44+/CD24- cells demonstrated enhanced progressive differentiation as well as showing a 60-fold increase in Matrigel invasion in both SKOV3 and OV90 cell lines (p < 0.001 each) compared to other phenotypes. CD44+/CD24- demonstrated significant resistance to all chemotherapy agents used in all cell lines, with a 71-93 % increase in resistance compared with baseline. Using a threshold of 25 % CD44+/CD24- ovarian cancer cells found in ascites, patients with > 25 % CD44+/CD24- were significantly more likely to recur (83 vs. 14 %, p = 0.003) and had shorter median progression-free survival (6 vs. 18 months, p = 0.01). In conclusion, the CD44+/CD24- phenotype in ovarian cancer cells demonstrate cancer stem cell-like properties of enhanced differentiation, invasion, and resistance to chemotherapy. This CD44+/CD24- phenotype correlates to clinical endpoints with increased risk of recurrence and shorter progression-free survival in patients with ovarian cancer.