Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models
Ioanna Keklikoglou,Chiara Cianciaruso,Esra Güç,Mario Leonardo Squadrito,Laura Spring,Simon Tazzyman,Lore Lambein,Amanda Poissonnier,Gino B. Ferraro,Caroline Baer,Antonino M. Cassarà,Alan Guichard,M. Luisa Iruela-Arispe,M. Luisa Iruela-Arispe,Claire E. Lewis,Lisa M. Coussens,Aditya Bardia,Rakesh K. Jain,Jeffrey W. Pollard,Jeffrey W. Pollard,Michele De Palma +20 more
TLDR
It is shown that two classes of cytotoxic drugs broadly employed in pre-operative (neoadjuvant) breast cancer therapy, taxanes and anthracyclines, elicit tumour-derived EVs with enhanced pro-metastatic capacity.Abstract:
Cytotoxic chemotherapy is an effective treatment for invasive breast cancer. However, experimental studies in mice also suggest that chemotherapy has pro-metastatic effects. Primary tumours release extracellular vesicles (EVs), including exosomes, that can facilitate the seeding and growth of metastatic cancer cells in distant organs, but the effects of chemotherapy on tumour-derived EVs remain unclear. Here we show that two classes of cytotoxic drugs broadly employed in pre-operative (neoadjuvant) breast cancer therapy, taxanes and anthracyclines, elicit tumour-derived EVs with enhanced pro-metastatic capacity. Chemotherapy-elicited EVs are enriched in annexin A6 (ANXA6), a Ca2+-dependent protein that promotes NF-κB-dependent endothelial cell activation, Ccl2 induction and Ly6C+CCR2+ monocyte expansion in the pulmonary pre-metastatic niche to facilitate the establishment of lung metastasis. Genetic inactivation of Anxa6 in cancer cells or Ccr2 in host cells blunts the pro-metastatic effects of chemotherapy-elicited EVs. ANXA6 is detected, and potentially enriched, in the circulating EVs of breast cancer patients undergoing neoadjuvant chemotherapy.read more
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Ayuko Hoshino,Bruno Costa-Silva,Tang-Long Shen,Gonçalo Rodrigues,Ayako Hashimoto,Milica Tesic Mark,Henrik Molina,Shinji Kohsaka,Angela Di Giannatale,Sophia Ceder,Swarnima Singh,Caitlin Williams,Nadine Soplop,Kunihiro Uryu,Lindsay A. Pharmer,Tari A. King,Linda Bojmar,Alexander E. Davies,Yonathan Ararso,Tuo Zhang,Haiying Zhang,Jonathan M. Hernandez,Joshua Mitchell Weiss,Vanessa D. Dumont-Cole,Kimberly Kramer,Leonard H. Wexler,Aru Narendran,Gary K. Schwartz,John H. Healey,Per Sandström,Knut Jørgen Labori,Elin H. Kure,Paul M. Grandgenett,Michael A. Hollingsworth,Maria de Sousa,Sukwinder Kaur,Maneesh Jain,Kavita Mallya,Surinder K. Batra,William R. Jarnagin,Mary S. Brady,Øystein Fodstad,Volkmar Müller,Klaus Pantel,Andy J. Minn,Mina J. Bissell,Benjamin A. Garcia,Yibin Kang,Yibin Kang,Vinagolu K. Rajasekhar,Cyrus M. Ghajar,Irina Matei,Héctor Peinado,Jacqueline Bromberg,Jacqueline Bromberg,David Lyden +55 more
TL;DR: It is demonstrated that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells.
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2016 update of the PRIDE database and its related tools
Juan Antonio Vizcaíno,Attila Csordas,Noemi del-Toro,José A. Dianes,Johannes Griss,Ilias Lavidas,Gerhard Mayer,Yasset Perez-Riverol,Florian Reisinger,Tobias Ternent,Qing Wei Xu,Rui Wang,Henning Hermjakob +12 more
TL;DR: The developments in PRIDE resources and related tools are summarized and a brief update on the resources under development 'PRIDE Cluster' and 'PRide Proteomes', which provide a complementary view and quality-scored information of the peptide and protein identification data available inPRIDE Archive are given.
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