Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models
| Autor: | Aditya Bardia, Lore Lambein, Rakesh K. Jain, Simon Tazzyman, Lisa M. Coussens, Mario Leonardo Squadrito, Laura Spring, Ioanna Keklikoglou, Alan Guichard, Claire E. Lewis, Michele De Palma, Chiara Cianciaruso, Jeffrey W. Pollard, Esra Güç, Antonino M. Cassarà, Gino B. Ferraro, M. Luisa Iruela-Arispe, Caroline Baer, Amanda Poissonnier |
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| Rok vydání: | 2018 |
| Předmět: |
Lung Neoplasms
Paclitaxel medicine.medical_treatment Mice Nude Mice Transgenic Breast Neoplasms Article Extracellular Vesicles 03 medical and health sciences 0302 clinical medicine Breast cancer Cell Movement Annexin Cell Line Tumor Animals Humans Medicine Cytotoxic T cell Annexin A6 Chemokine CCL2 Neoplastic Processes 030304 developmental biology Mice Knockout 0303 health sciences Chemotherapy business.industry Monocyte Mammary Neoplasms Experimental Cell Biology medicine.disease Microvesicles 3. Good health Cell biology Mice Inbred C57BL Protein Transport medicine.anatomical_structure Doxorubicin 030220 oncology & carcinogenesis Cancer cell Cancer research Experimental pathology Female business |
| Zdroj: | Keklikoglou, I, Cianciaruso, C, Guc, E, Squadrito, M L, Spring, L M, Tazzyman, S, Lambein, L, Poissonnier, A, Ferraro, G B, Baer, C, Cassara, A, Guichard, A, Iruela-Arispe, M L, Lewis, C E, Coussens, L M, Bardia, A, Jain, R K, Pollard, J W & De Palma, M 2019, ' Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models ', Nature Cell Biology, vol. 21, no. 2, pp. 190–202 . https://doi.org/10.1038/s41556-018-0256-3 Nature Cell Biology |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/s41556-018-0256-3 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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