CD133 expression in circulating tumor cells from breast cancer patients: Potential role in resistance to chemotherapy
CD133 expression in circulating tumor cells from breast cancer patients: Potential role in resistance to chemotherapy
复制标题
DOI：
10.1002/ijc.28263
复制
发表时间：
2013-11-15
影响因子：
6.4
通讯作者：
Jose Serrano, M.
中科院分区：
文献类型：
--
作者：
Nadal, Rosa;Gabriel Ortega, F.;Jose Serrano, M.
CD133与细胞特性相关，如自我更新、迁移和血管生成模拟，可能参与循环肿瘤细胞（ctc）的产生。我们在98例非转移性乳腺癌（BC）患者的ctc中鉴定了CD133的表达。采用免疫磁珠技术分离ctc，磁珠上标记有多细胞角蛋白（CK）特异性抗体（CK3-11D5），免疫细胞化学方法检测ctc和CD133。65%的患者在基线时发现CK+/CD133(+) CTCs，在全身治疗后发现47.8% （p = 0.53）。研究CTCs中CD133的状态与典型临床病理特征和治疗反应的相关性。Her2未扩增和Ki-67指数低与CK+/CD133(+) ctc的存在呈正相关。在任何治疗之前，CK+/CD133(+) ctc在腔内BC亚型患者中更常见。全身治疗后，CK+/CD133(+) CTCs和BC亚型的比例无统计学差异，这表明在三阴性和her2扩增肿瘤中CK+/CD133(+) CTCs相对富集。当分析整个人群时，化疗后CK+/ ctc降低，而CK+/CD133(+) ctc在非腔内BC亚型治疗后样本中富集。这些发现提示CD133作为非腔内BC患者化疗耐药标志物的潜在作用。需要进一步的前瞻性研究和广泛的临床前模型来确认CD133是否是化疗耐药的标记物，以及它作为靶向癌症干细胞和肿瘤血管的新型抗癌疗法的靶点的作用。有什么新鲜事吗?尽管乳腺癌治疗取得了进展，但对癌症治疗的原发性和获得性耐药性仍然是一个挑战。在这里，作者观察了与干细胞和迁移特性以及非转移性患者血管源性mimicryin循环肿瘤细胞（ctc）相关的CD133a糖蛋白的表达。CD133广泛表达，特别是在接受治疗前的腔内肿瘤患者中。在全身治疗后的非腔内肿瘤亚型中检测到CD133+ ctc的相对富集，提示CD133+ ctc在化疗耐药中的潜在作用。CTCs中CD133的特征可能有助于开发针对癌症干细胞和肿瘤血管系统的新治疗方法。
CD133 has been associated with cell properties such as self renewal, migration and vasculogenic mimicry, potentially involved in generation of circulating tumor cells (CTCs). We characterized CD133 expression in CTCs of 98 nometastatic breast cancer (BC) patients. CTCs were isolated by immunomagnetic techniques using magnetic beads labeled with a multicytokeratin(CK)-specific antibody (CK3-11D5) and CTCs and CD133 detection through immunocytochemical methods. CK+/CD133(+) CTCs were identified in 65% of patients at baseline and 47.8% after systemic therapy (p = 0.53). Correlation of CD133 status in CTCs with classical clinicopathological characteristics and response to therapy was performed. Her2 not amplified and low Ki-67 index were positively correlated with presence of CK+/CD133(+) CTCs. Before any treatment, CK+/CD133(+) CTCs were more frequently isolated in patients with luminal BC subtype. No statistically significant differences were found between proportion of CK+/CD133(+) CTCs and BC subtypes after systemic therapy, implying a relative enrichment of CK+/CD133(+) CTCs in triple negative and HER2-amplified tumors. While CK+/CTCs decreases after chemotherapy when analyzing the whole population, CK+/CD133(+) CTCs were enriched in post-treatment samples in nonluminal BC subtypes. These findings suggest the potential role of CD133 as a promising marker of chemoresistance in nonluminal BC patients. Further prospective studies and extensive preclinical modeling will be needed to confirm whether CD133 is a marker of resistance to chemotherapy, and its role as a target for novel anticancer therapies targeting cancer stem cells and tumor vasculature.What's new? Despite advances in breast cancer treatments, primary and acquired resistance to cancer therapies remains a challenge. Here the authors looked at the expression of CD133a glycoprotein associated with stem cell and migratory properties and vasculogenic mimicryin circulating tumor cells (CTCs) of non-metastatic patients. CD133 was widely expressed, particularly in patients with luminal tumors before they received treatment. A relative enrichment was detected in non-luminal tumor subtypes following systemic therapy, suggesting a potential role of CD133+ CTCs in chemoresistance. Characterization of CD133 in CTCs might help to develop new therapeutic approaches targeting cancer stem cells and tumor vasculature.