Hypoxia stimulates CTC-platelet cluster formation to promote breast cancer metastasis

作者：Weijia Zhou, Chengjun Zhu, Peiliang Shen, Jacqueline Wang, Gaoshuang Zhu, Yuanyuan Jia, Yueyao Wu, Siliang Wang, Jia Sun, Fang Yang, Yanni Song, Xin Han, Xiaoxiang Guan · 发表于：iScience · 年份：2024 · DOI：10.1016/j.isci.2024.109547 · 被引用次数：11 · 研究领域：Cancer Cells and Metastasis、Cancer Genomics and Diagnostics、Cancer, Hypoxia, and Metabolism

Circulating tumor cell clusters/micro-emboli (CTM) possess greater metastatic capacity and survival advantage compared to individual circulating tumor cell (CTC). However, the formation of CTM subtypes and their role in tumor metastasis remain unclear. In this study, we used a microfluidic Cluster-Chip with easy operation and high efficiency to isolate CTM from peripheral blood, which confirmed their correlation with clinicopathological features and identified the critical role of CTC-platelet clusters in breast cancer metastasis. The correlation between platelets and CTM function was further confirmed in a mouse model and RNA sequencing of CTM identified high-expressed genes related to hypoxia stimulation and platelet activation which possibly suggested the correlation of hypoxia and CTC-platelet cluster formation. In conclusion, we successfully developed the Cluster-Chip platform to realize the clinical capture of CTMs and analyze the biological properties of CTC-platelet clusters, which could benefit the design of potential treatment regimens to prevent CTM-mediated metastasis and tumor malignant progression.