静脉注射
缺氧(环境)
细胞生物学
生物
癌症研究
作者
Cinzia Donato,Leo Kunz,Francesc Castro-Giner,Aino Paasinen-Sohns,Karin Strittmatter,Barbara Maria Szczerba,Ramona Scherrer,Nunzia Di Maggio,Wolf Heusermann,Oliver Biehlmaier,Christian Beisel,Marcus Vetter,Christoph Rochlitz,Walter P. Weber,Andrea Banfi,Timm Schroeder,Nicola Aceto
出处
期刊:Cell Reports
[Elsevier]
日期:2020-09-08
卷期号:32 (10): 108105-108105
被引量:64
标识
DOI:10.1016/j.celrep.2020.108105
摘要
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.
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