Institute of Pathology, Heidelberg University, 69120 Heidelberg, Germany.
Hum Pathol. 2010 Apr;41(4):574-81. doi: 10.1016/j.humpath.2009.08.023. Epub 2009 Dec 11.
Breast cancer cells with the CD44(+)/CD24(-) phenotype have been associated with stem cell properties. To analyze effects of cytotoxic chemotherapy on these cells, we examined a series of 50 breast carcinomas before and after neoadjuvant chemotherapy with epirubicin/cyclophosphamide using double immunofluorescence. Before treatment, an average of 4.4% of the tumor cells displayed a CD44(+)/CD24(-) phenotype. However, after chemotherapy, the frequency of CD44(+)/CD24(-) cells dropped to 2% (P = .008). To test this unexpected finding, we analyzed a second collective of 16 patients that preoperatively had received either 4 cycles of doxorubicin/pemetrexed, followed by 4 cycles of docetaxel or 4 cycles of doxorubicin/cyclophosphamide, followed by 4 cycles of docetaxel with similar results (8.7% CD44(+)/CD24(-) cells on average before and 1.1% after chemotherapy). In addition, no association was observed between the frequency of CD44(+)/CD24(-) cells and the response to chemotherapy or patient survival. However, patients with tumors containing high numbers of CD44(+)/CD24(-) cells more frequently developed bone metastases in the course of disease. In conclusion, our findings challenge the proposed role of CD44(+)/CD24(-) cells as cancer stem cells in tumor resistance to chemotherapy as they apparently are not selected by conventional cytotoxic agents.
乳腺癌细胞具有 CD44(+)/CD24(-) 表型，与干细胞特性相关。为了分析细胞毒性化疗对这些细胞的影响，我们使用双重免疫荧光法，在新辅助化疗（表阿霉素/环磷酰胺）前后，对 50 例乳腺癌进行了一系列检查。治疗前，平均有 4.4%的肿瘤细胞呈现 CD44(+)/CD24(-) 表型。然而，化疗后，CD44(+)/CD24(-) 细胞的频率降至 2%（P =.008）。为了验证这一意外发现，我们分析了第二组 16 例患者的资料，这些患者术前分别接受了 4 个周期的多柔比星/培美曲塞，然后是 4 个周期的多西紫杉醇，或者接受了 4 个周期的多柔比星/环磷酰胺，然后是 4 个周期的多西紫杉醇，结果相似（化疗前平均有 8.7%的 CD44(+)/CD24(-) 细胞，化疗后有 1.1%）。此外，CD44(+)/CD24(-) 细胞的频率与化疗反应或患者生存之间没有关联。然而，含有大量 CD44(+)/CD24(-) 细胞的肿瘤患者在疾病过程中更频繁地发生骨转移。总之，我们的发现对 CD44(+)/CD24(-) 细胞作为肿瘤对化疗耐药的癌症干细胞的作用提出了挑战，因为它们显然不是常规细胞毒性药物选择的。
