Authors
Héctor Peinado, Maša Alečković, Simon Lavotshkin, Irina Matei, Bruno Costa-Silva, Gema Moreno-Bueno, Marta Hergueta-Redondo, Caitlin Williams, Guillermo García-Santos, Cyrus M Ghajar, Ayuko Nitadori-Hoshino, Caitlin Hoffman, Karen Badal, Benjamin A Garcia, Margaret K Callahan, Jianda Yuan, Vilma R Martins, Johan Skog, Rosandra N Kaplan, Mary S Brady, Jedd D Wolchok, Paul B Chapman, Yibin Kang, Jacqueline Bromberg, David Lyden
Publication date
2012/6
Journal
Nature medicine
Volume
18
Issue
6
Pages
883-891
Publisher
Nature Publishing Group
Description
Tumor-derived exosomes are emerging mediators of tumorigenesis. We explored the function of melanoma-derived exosomes in the formation of primary tumors and metastases in mice and human subjects. Exosomes from highly metastatic melanomas increased the metastatic behavior of primary tumors by permanently'educating'bone marrow progenitors through the receptor tyrosine kinase MET. Melanoma-derived exosomes also induced vascular leakiness at pre-metastatic sites and reprogrammed bone marrow progenitors toward a pro-vasculogenic phenotype that was positive for c-Kit, the receptor tyrosine kinase Tie2 and Met. Reducing Met expression in exosomes diminished the pro-metastatic behavior of bone marrow cells. Notably, MET expression was elevated in circulating CD45− C-KIT low/+ TIE2+ bone marrow progenitors from individuals with metastatic melanoma. RAB1A, RAB5B, RAB7 and …
Total citations
Scholar articles
Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET
H Peinado, M Alečković, S Lavotshkin, I Matei… - Nature medicine, 2012