Dissecting the Heterogeneity of Circulating Tumor Cells in Metastatic Breast Cancer: Going Far Beyond the Needle in the Haystack.

Dissecting the Heterogeneity of Circulating Tumor Cells in Metastatic Breast Cancer: Going Far Beyond the Needle in the Haystack.
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DOI:
10.3390/ijms17101775
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发表时间:
2016-10-24
影响因子:
5.6
通讯作者:
Cesselli D
Cesselli D
中科院分区:
生物学2区
文献类型:
--
作者:
Bulfoni M;Turetta M;Del Ben F;Di Loreto C;Beltrami AP;Cesselli D

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尽管定义为表达上皮细胞粘附分子和细胞角蛋白(EpCAM+/CK+)的循环肿瘤细胞(CTC)的计数可以预测转移性乳腺癌、结肠癌和前列腺癌的预后和对治疗的反应,但其临床实用性(即,通过指导治疗来改善患者结果的能力)尚未在临床试验中得到证实。因此,科学家们现在专注于CTC的分子表征,以探索其作为肿瘤组织“替代物”的可能用途,以非侵入性地评估癌症的基因组景观及其在治疗期间的演变。此外,有证据证实CTC在上皮-间质转化(EMT)中的存在,其特征在于上皮标志物的可变损失。由于EMT过程可以产生具有增强的侵袭性、干细胞性和耐药性的细胞,因此该群体的计数和表征(也许是真正负责肿瘤复发和进展的群体)可能在临床上更有用。由于这些原因,已经开发了几种能够独立于上皮标志物的表达捕获CTC的装置。在这篇综述中,我们将描述到目前为止发现的异质性类型和上皮细胞向间充质细胞转化在驱动CTC异质性中发挥的关键作用。还将讨论检测CTC异质性的临床相关性。
Although the enumeration of circulating tumor cells (CTC) defined as expressing both epithelial cell adhesion molecule and cytokeratins (EpCAM+/CK+) can predict prognosis and response to therapy in metastatic breast, colon and prostate cancer, its clinical utility (i.e., the ability to improve patient outcome by guiding therapy) has not yet been proven in clinical trials. Therefore, scientists are now focusing on the molecular characterization of CTC as a way to explore its possible use as a “surrogate” of tumor tissues to non-invasively assess the genomic landscape of the cancer and its evolution during treatment. Additionally, evidences confirm the existence of CTC in epithelial-to-mesenchymal transition (EMT) characterized by a variable loss of epithelial markers. Since the EMT process can originate cells with enhanced invasiveness, stemness and drug-resistance, the enumeration and characterization of this population, perhaps the one truly responsible of tumor recurrence and progression, could be more clinically useful. For these reasons, several devices able to capture CTC independently from the expression of epithelial markers have been developed. In this review, we will describe the types of heterogeneity so far identified and the key role played by the epithelial-to-mesenchymal transition in driving CTC heterogeneity. The clinical relevance of detecting CTC-heterogeneity will be discussed as well.
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