Pershina Olga, Ermakova Natalia, Pakhomova Angelina, Widera Darius, Pan Edgar, Zhukova Mariia, Slonimskaya Elena, Morozov Sergey G, Kubatiev Aslan, Dygai Alexander, Skurikhin Evgenii G
Laboratory of Regenerative Pharmacology, Goldberg ED Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Centre of the Russian Academy of Sciences, Lenin, 3, 634028 Tomsk, Russia.
Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights Campus, Reading RG6 6AP, UK.
Biomedicines. 2021 Sep 14;9(9):1223. doi: 10.3390/biomedicines9091223.
New drug targets, markers of disease prognosis, and more efficient treatment options are an unmet clinical need in breast cancer (BC). We have conducted a pilot study including patients with luminal B stage breast cancer IIA-IIIB. The presence and frequency of various populations of cancer stem cells (CSC) and somatic stem cells were assessed in the blood, breast tumor tissue, and normal breast tissue. Our results suggest that patients with BC can be divided into two distinct groups based on the frequency of aldehyde dehydrogenase positive cells (ALDH1 cells) in the blood (ALDH1 and ALDH1). In the ALDH1 cells group, the tumor is dominated by epithelial tumor cells CD44CD24, CD326CD44CD24, and CD326CD49f, while in the ALDH1 cells group, CSCs of mesenchymal origin and epithelial tumor cells (CD227CD44CD24 and CD44CD24CD49f) are predominant. In vitro CSCs of the ALDH1 cells group expressing CD326 showed high resistance to cytostatics, CD227 CSCs of the ALDH1 cells group are sensitive to cytostatics. Epithelial precursors of a healthy mammary gland were revealed in normal breast tissue of patients with BC from both groups. The cells were associated with a positive effect of chemotherapy and remission in BC patients. Thus, dynamic control of their presence in blood and assessment of the sensitivity of CSCs to cytostatics in vitro can improve the effectiveness of chemotherapy in BC.
新的药物靶点、疾病预后标志物以及更有效的治疗方案是乳腺癌（BC）尚未满足的临床需求。我们开展了一项试点研究，纳入了IIA-IIIB期管腔B型乳腺癌患者。评估了血液、乳腺肿瘤组织和正常乳腺组织中各种癌症干细胞（CSC）和体细胞干细胞群体的存在情况及频率。我们的结果表明，根据血液中醛脱氢酶阳性细胞（ALDH1细胞）的频率，BC患者可分为两个不同的组（ALDH1⁺和ALDH1⁻）。在ALDH1⁺细胞组中，肿瘤以上皮肿瘤细胞CD44⁺CD24⁻、CD326⁺CD44⁺CD24⁻和CD326⁺CD49f⁺为主，而在ALDH1⁻细胞组中，间充质来源的CSC和上皮肿瘤细胞（CD227⁺CD44⁺CD24⁻和CD44⁺CD24⁻CD49f⁺）占主导。体外实验中，ALDH1⁺细胞组中表达CD326的CSC对细胞抑制剂具有高抗性，ALDH1⁻细胞组的CD227⁺CSC对细胞抑制剂敏感。在两组BC患者的正常乳腺组织中均发现了健康乳腺的上皮前体细胞。这些细胞与BC患者化疗的积极效果和缓解相关。因此，动态监测它们在血液中的存在情况以及评估体外CSC对细胞抑制剂的敏感性，可以提高BC化疗的效果。
