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

Weijia Zhou; Chengjun Zhu; Peiliang Shen; Jacqueline F Wang; Gaoshuang Zhu; Yuanyuan Jia; Yueyao Wu; Siliang Wang; Jia Sun; Fang Yang; Yanni Song; Xin Han; Xiaoxiang Guan

doi:10.1016/j.isci.2024.109547

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

iScience. 2024 Mar 20;27(5):109547. doi: 10.1016/j.isci.2024.109547. eCollection 2024 May 17.

Authors

Weijia Zhou¹, Chengjun Zhu², Peiliang Shen¹, Jacqueline F Wang³, Gaoshuang Zhu¹, Yuanyuan Jia¹, Yueyao Wu¹, Siliang Wang⁴, Jia Sun¹, Fang Yang⁵, Yanni Song⁶, Xin Han¹, Xiaoxiang Guan²

Affiliations

¹ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine & Holistic Integrative Medicine, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
² Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
³ Department of Medicine, NYU Langone Health, 550 First Avenue, New York, NY 10016, USA.
⁴ Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
⁵ The Comprehensive cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
⁶ Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin 150081, China.

Abstract

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.

Keywords: Biotechnology; Cancer; Cell biology.