Hypoxia Triggers the Intravasation of Clustered Circulating Tumor Cells

Donato, Cinzia and Kunz, Leo and Castro-Giner, Francesc and Paasinen-Sohns, Aino and Strittmatter, Karin and Szczerba, Barbara Maria and Scherrer, Ramona and Di Maggio, Nunzia and Heusermann, Wolf and Biehlmaier, Oliver and Beisel, Christian and Vetter, Marcus and Rochlitz, Christoph and Weber, Walter Paul and Banfi, Andrea and Schroeder, Timm and Aceto, Nicola. (2020) Hypoxia Triggers the Intravasation of Clustered Circulating Tumor Cells. Cell reports, 32 (10). p. 108105.

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Official URL: https://edoc.unibas.ch/78597/

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Circulating tumor cells (CTCs) are shed from solid cancers in the form of single or clustered cells, and the latter display an extraordinary ability to initiate metastasis. Yet, the biological phenomena that trigger the shedding of CTC clusters from a primary cancerous lesion are poorly understood. Here, when dynamically labeling breast cancer cells along cancer progression, we observe that the majority of CTC clusters are undergoing hypoxia, while single CTCs are largely normoxic. Strikingly, we find that vascular endothelial growth factor (VEGF) targeting leads to primary tumor shrinkage, but it increases intra-tumor hypoxia, resulting in a higher CTC cluster shedding rate and metastasis formation. Conversely, pro-angiogenic treatment increases primary tumor size, yet it dramatically suppresses the formation of CTC clusters and metastasis. Thus, intra-tumor hypoxia leads to the formation of clustered CTCs with high metastatic ability, and a pro-angiogenic therapy suppresses metastasis formation through prevention of CTC cluster generation.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cell and Gene Therapy (Banfi)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Imaging Core Facility (Biehlmaier)
UniBasel Contributors:Biehlmaier, Oliver and Banfi, Andrea
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:02 Nov 2020 09:40
Deposited On:02 Nov 2020 09:40

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