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Disseminated tumour cells in bone marrow are the source of cancer relapse after therapy

机译:骨髓中扩散的肿瘤细胞是治疗后癌症复发的根源

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Accumulating evidence indicates that cancer cells spread much earlier than was previously believed. Recent technological advances have greatly improved the detection methods of circulating tumour cells (CTCs), suggesting that the dissemination of cancer cells into the circulation occurs randomly. Most CTCs die in circulation as a result of shear stress and/or anoikis. However, the persistence of disseminated tumour cells (DTCs) in the bone marrow is the result of interaction of DTCs with bone marrow microenvironment. DTCs in the bone marrow undergo successive clonal expansions and a parallel progression that leads to new variants. Compared to the CTCs, DTCs in the bone marrow have a unique signature, which displayed dormant, mesenchymal phenotype and osteoblast‐like or osteoclast‐like phenotype. The persistence of DTCs in the bone marrow is always related to minimal residual diseases (MRDs). This review outlines the difference between CTCs and DTCs in the bone marrow and describes how this difference affects the clinical values of CTCs and DTCs, such as metastasis and recurrence. We suggest that DTCs remaining in the bone marrow after therapy can be used as a superior marker in comparison with CTCs to define patients with an unfavourable prognosis and may therefore be a potential prognostic factor and therapeutic target for cancer therapy.
机译:越来越多的证据表明,癌细胞的扩散要比以前认为的要早得多。最近的技术进步极大地改善了循环肿瘤细胞(CTC)的检测方法,表明癌细胞向循环中的扩散是随机发生的。大多数四氯化碳由于剪切应力和/或阳极失灵而在循环中死亡。但是,骨髓中弥散性肿瘤细胞(DTC)的持久性是DTC与骨髓微环境相互作用的结果。骨髓中的DTC经过连续的克隆扩增和平行进展,从而导致新的变异。与CTC相比,骨髓中的DTC具有独特的特征,表现出休眠,间充质表型和成骨细胞样或破骨细胞样表型。 DTC在骨髓中的持久性始终与最小残留疾病(MRD)有关。这篇综述概述了骨髓中CTC和DTC之间的差异,并描述了这种差异如何影响CTC和DTC的临床价值,例如转移和复发。我们建议,与CTC相比,治疗后残留在骨髓中的DTC可以用作优越的标志物,以定义预后不良的患者,因此可能成为癌症治疗的潜在预后因素和治疗目标。

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