Functional Analysis of Viable Circulating Tumor Cells from Triple-Negative Breast Cancer Patients Using TetherChip Technology.
Functional Analysis of Viable Circulating Tumor Cells from Triple-Negative Breast Cancer Patients Using TetherChip Technology.
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DOI：
10.3390/cells12151940
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发表时间：
2023-07-26
期刊：
影响因子：
6
通讯作者：
Kallergi, Galatea
中科院分区：
文献类型：
--
作者：
Vardas, Vasileios;Ju, Julia A.;Christopoulou, Athina;Xagara, Anastasia;Georgoulias, Vassilis;Kotsakis, Athanasios;Alix-Panabieres, Catherine;Martin, Stuart S.;Kallergi, Galatea
大约90%的乳腺癌患者死亡是由于转移，而不是原发肿瘤的生长。微触须（McTNs）的形成是肿瘤转移的重要机制。三阴性乳腺癌（TNBC）是最具侵袭性的亚型，靶向治疗有限。本研究旨在分离活的循环肿瘤细胞（CTCs），并分析其对药物治疗的功能反应。从20例TNBC患者中分离ctc并在培养中维持5天。通过免疫荧光染色和VyCap分析确定生物标志物的表达。通过检测m30阳性细胞来评价长春瑞滨诱导的细胞凋亡。我们的研究结果显示，与患者细胞自旋中的CTC数量相比，使用TetherChips分析的CTC绝对数量显著增加（p = 0.006），为药物评估提供了足够的肿瘤细胞。长春瑞滨治疗活CTCs （1 h）可显著诱导细胞凋亡（p = 0.010）。它还引起去酪氨酸α-微管蛋白（GLU）、表达程序性死亡配体（PD-L1）的ctc的显著减少（p < 0.001）和mctn的破坏。总之，这项试点研究提供了一个有用的方案，使用TetherChip技术对活体ctc进行功能分析和药物疗效评估，为在患者个体化水平上靶向转移性传播提供了重要信息。
Metastasis, rather than the growth of the primary tumor, accounts for approximately 90% of breast cancer patient deaths. Microtentacles (McTNs) formation represents an important mechanism of metastasis. Triple-negative breast cancer (TNBC) is the most aggressive subtype with limited targeted therapies. The present study aimed to isolate viable circulating tumor cells (CTCs) and functionally analyze them in response to drug treatment. CTCs from 20 TNBC patients were isolated and maintained in culture for 5 days. Biomarker expression was identified by immunofluorescence staining and VyCap analysis. Vinorelbine-induced apoptosis was evaluated based on the detection of M30-positive cells. Our findings revealed that the CTC absolute number significantly increased using TetherChips analysis compared to the number of CTCs in patients’ cytospins (p = 0.006) providing enough tumor cells for drug evaluation. Vinorelbine treatment (1 h) on live CTCs led to a significant induction of apoptosis (p = 0.010). It also caused a significant reduction in Detyrosinated α-tubulin (GLU), programmed death ligand (PD-L1)-expressing CTCs (p < 0.001), and disruption of McTNs. In conclusion, this pilot study offers a useful protocol using TetherChip technology for functional analysis and evaluation of drug efficacy in live CTCs, providing important information for targeting metastatic dissemination at a patient-individualized level.
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影响因子：
5.2
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作者：
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Martin SS
影响因子：
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通讯作者：
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影响因子：
4.7
作者：
Parker AL;Kavallaris M;McCarroll JA
通讯作者：
McCarroll JA