PUBLICATION ALERT : Nature Cell Biology - EPFL - Lausanne.

Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models

In this high impact scientific communication the authors demonstrate how, contrary to expectations, the two chemotherapy agents, Paclitaxel (PTX) and Doxorubicin (DOX) can promote tumor metastasis by inducing release of extracellular vesicles (EVs) from primary tumors. They used the PhotonIMAGERTMOPTIMA to demonstrate increased tumour growth in WT mice pre-conditioned with EVs prepared from 4T1 tumor bearing mice, which had been treated with PTX (PTX-EVs) compared to control CREMO-EVs. In contrast, Ccr2-KO mice did not show increase tumor growth when treated with PTX-EVs, thus suggesting a role for monocyte chemotaxis in PTX-EV mediated tumour enhancement. The researchers also observed enrichment of the Ca2+-dependant membrane-binding protein Annexin A6 (ANXA6) in PTX-EVs and DOX-EVs. ANXA6 is known to regulate membrane trafficking and cell signalling. The team then showed that the pro-metastatic capacity of chemotherapy-elicited EVs was dependent on Ly6C+CCR2+ monocytes and Annexin VI expression.

Ioanna Keklikoglou, Chiara Cianciaruso, Esra Güç2, Mario Leonardo Squadrito, Laura M. Spring3, Simon Tazzyman, Lore Lambein, Amanda Poissonnier, Gino B. Ferraro, Caroline Baer, Antonino Cassará, Alan Guichard, M. Luisa Iruela-Arispe, Claire E. Lewis,Lisa M. Coussens, Aditya Bardia, Rakesh K. Jain, Jeffrey W. Pollard and Michele De Palma

DOI: 10.1038/s41556-018-0256-3
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