Chemotherapy-induced release of circulating-tumor cells into the bloodstream in collective migration units with cancer-associated fibroblasts in metastatic cancer patients
Chemotherapy-induced release of circulating-tumor cells into the bloodstream in collective migration units with cancer-associated fibroblasts in metastatic cancer patients
复制标题
DOI：
10.1186/s12885-020-07376-1
复制
发表时间：
2020-09-11
期刊：
影响因子：
3.8
通讯作者：
King, Michael R.
中科院分区：
文献类型：
--
作者：
Ortiz-Otero, Nerymar;Marshall, Jocelyn R.;King, Michael R.
背景 最近的研究表明，化疗会破坏血管系统的稳定性，并增加循环肿瘤细胞 (CTC) 流入转移性癌症患者 (Met-pa) 的循环。 CTC 是癌症转移的前兆，它们可以作为单个 CTC 或作为与癌症相关成纤维细胞 (CAF) 等基质细胞一起作为细胞聚集体的 CTC 簇迁移。方法采集52例Met-pa的血样，测定CTC和CAF的数量以及化疗过程中CTC和CAF的时间波动。结果在本研究中，发现CTC水平在1个周期的化疗后从初始水平增加两倍，并在2个周期的化疗后恢复到基线。重要的是，我们首次确定循环 CAF 水平与 Met-pa 患者预后较差和生存概率较低相关。根据化疗诱导的 CTC 释放，我们评估了之前开发的癌症免疫疗法使用离体方法从 Met-pa 血液中消除 CTC 的功效，并证明这可以杀死超过 60% 的 CTC。结论 总的来说，我们发现 Met-pa 中的 CAF 水平可作为癌症预后的预测生物标志物。此外，我们还证明了我们的疗法能够杀死多种癌症类型的原发性 CTC，支持其在临床环境中作为抗转移疗法的潜在用途。
Background Recent studies have shown that chemotherapy destabilizes the blood vasculature and increases circulating tumor cell (CTC) influx into the circulation of metastatic cancer patients (Met-pa). CTCs are a precursor of cancer metastasis, in which they can migrate as single CTCs or as CTC clusters with stromal cells such as cancer-associated fibroblasts (CAFs) as cell aggregates. Methods Blood samples were collected from 52 Met-pa, and the number of CTC and CAF was determined along with the temporal fluctuation of these through the chemotherapy treatment. Results In this study, CTC level was found to increase two-fold from the initial level after 1 cycle of chemotherapy and returned to baseline after 2 cycles of chemotherapy. Importantly, we determined for the first time that circulating CAF levels correlate with worse prognosis and a lower probability of survival in Met-pa. Based on the CTC release induced by chemotherapy, we evaluated the efficacy of our previously developed cancer immunotherapy to eradicate CTCs from Met-pa blood using an ex vivo approach and demonstrate this could kill over 60% of CTCs. Conclusion Collectively, we found that CAF levels in Met-pa serve as a predictive biomarker for cancer prognosis. Additionally, we demonstrate the efficacy of our therapy to kill primary CTCs for a range of cancer types, supporting its potential use as an anti-metastasis therapy in the clinical setting.