Department of Genetics, Cancer Research Institute, Biomedical Research Center of Slovak Academy of Sciences, 84505 Bratislava, Slovakia.
Int J Mol Sci. 2022 Oct 12;23(20):12141. doi: 10.3390/ijms232012141.
Metastatic breast cancer (MBC) is typically an incurable disease with high mortality rates; thus, early identification of metastatic features and disease recurrence through precise biomarkers is crucial. Circulating tumor cells (CTCs) consisting of heterogeneous subpopulations with different morphology and genetic, epigenetic, and gene expression profiles represent promising candidate biomarkers for metastatic potential. The experimentally verified role of epithelial-to-mesenchymal transition in cancer dissemination has not been clearly described in BC patients, but the stemness features of CTCs strongly contributes to metastatic potency. Single CTCs have been shown to be protected in the bloodstream against recognition by the immune system through impaired interactions with T lymphocytes and NK cells, while associations of heterotypic CTC clusters with platelets, leucocytes, neutrophils, tumor-associated macrophages, and fibroblasts improve their tumorigenic behavior. In addition to single CTC and CTC cluster characteristics, we reviewed CTC evaluation methods and clinical studies in early and metastatic BCs. The variable CTC tests were developed based on specific principles and strategies. However, CTC count and the presence of CTC clusters were shown to be most clinically relevant in existing clinical trials. Despite the known progress in CTC research and sampling of BC patients, implementation of CTCs and CTC clusters in routine diagnostic and treatment strategies still requires improvement in detection sensitivity and precise molecular characterizations, focused predominantly on the role of CTC clusters for their higher metastatic potency.
转移性乳腺癌（MBC）通常是一种不可治愈的疾病，死亡率很高；因此，通过精确的生物标志物早期识别转移特征和疾病复发至关重要。由具有不同形态和遗传、表观遗传以及基因表达谱的异质亚群组成的循环肿瘤细胞（CTC）是具有转移潜力的有前途的候选生物标志物。上皮-间充质转化在乳腺癌患者中的癌症扩散中的作用虽然在实验中得到了验证，但 CTC 的干性特征强烈有助于转移能力。已经表明，通过与 T 淋巴细胞和 NK 细胞的相互作用受损，单个 CTC 在血液中免受免疫系统的识别而受到保护，而异质 CTC 簇与血小板、白细胞、中性粒细胞、肿瘤相关巨噬细胞和成纤维细胞的关联则增强了它们的致瘤行为。除了单个 CTC 和 CTC 簇特征外，我们还回顾了早期和转移性 BC 中的 CTC 评估方法和临床研究。可变的 CTC 检测基于特定的原理和策略进行开发。然而，在现有的临床试验中，CTC 计数和 CTC 簇的存在被证明与临床相关性最强。尽管在 CTC 研究和 BC 患者采样方面取得了已知的进展，但在常规诊断和治疗策略中实施 CTC 和 CTC 簇仍需要提高检测灵敏度和精确的分子特征，主要集中在 CTC 簇在其更高的转移潜力方面的作用。
