Nature cell biology, 2015-06, Vol.17 (6), p.816-826
- Costa-Silva, Bruno
- Aiello, Nicole M
- Ocean, Allyson J
- Singh, Swarnima
- Zhang, Haiying
- Thakur, Basant Kumar
- Becker, Annette
- Hoshino, Ayuko
- Mark, Milica Tešić
- Molina, Henrik
- Xiang, Jenny
- Zhang, Tuo
- Theilen, Till-Martin
- García-Santos, Guillermo
- Williams, Caitlin
- Ararso, Yonathan
- Huang, Yujie
- Rodrigues, Gonçalo
- Shen, Tang-Long
- Labori, Knut Jørgen
- Lothe, Inger Marie Bowitz
- Kure, Elin H
- Hernandez, Jonathan
- Doussot, Alexandre
- Ebbesen, Saya H
- Grandgenett, Paul M
- Hollingsworth, Michael A
- Jain, Maneesh
- Mallya, Kavita
- Batra, Surinder K
- Jarnagin, William R
- Schwartz, Robert E
- Matei, Irina
- Peinado, Héctor
- Stanger, Ben Z
- Bromberg, Jacqueline
- Lyden, David
2015
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- Autor(en) / Beteiligte
- Costa-Silva, Bruno
- Aiello, Nicole M
- Ocean, Allyson J
- Singh, Swarnima
- Zhang, Haiying
- Thakur, Basant Kumar
- Becker, Annette
- Hoshino, Ayuko
- Mark, Milica Tešić
- Molina, Henrik
- Xiang, Jenny
- Zhang, Tuo
- Theilen, Till-Martin
- García-Santos, Guillermo
- Williams, Caitlin
- Ararso, Yonathan
- Huang, Yujie
- Rodrigues, Gonçalo
- Shen, Tang-Long
- Labori, Knut Jørgen
- Lothe, Inger Marie Bowitz
- Kure, Elin H
- Hernandez, Jonathan
- Doussot, Alexandre
- Ebbesen, Saya H
- Grandgenett, Paul M
- Hollingsworth, Michael A
- Jain, Maneesh
- Mallya, Kavita
- Batra, Surinder K
- Jarnagin, William R
- Schwartz, Robert E
- Matei, Irina
- Peinado, Héctor
- Stanger, Ben Z
- Bromberg, Jacqueline
- Lyden, David
- Titel
- Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver
- Ist Teil von
- Nature cell biology, 2015-06, Vol.17 (6), p.816-826
- Ort / Verlag
- England
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Pancreatic ductal adenocarcinomas (PDACs) are highly metastatic with poor prognosis, mainly due to delayed detection. We hypothesized that intercellular communication is critical for metastatic progression. Here, we show that PDAC-derived exosomes induce liver pre-metastatic niche formation in naive mice and consequently increase liver metastatic burden. Uptake of PDAC-derived exosomes by Kupffer cells caused transforming growth factor β secretion and upregulation of fibronectin production by hepatic stellate cells. This fibrotic microenvironment enhanced recruitment of bone marrow-derived macrophages. We found that macrophage migration inhibitory factor (MIF) was highly expressed in PDAC-derived exosomes, and its blockade prevented liver pre-metastatic niche formation and metastasis. Compared with patients whose pancreatic tumours did not progress, MIF was markedly higher in exosomes from stage I PDAC patients who later developed liver metastasis. These findings suggest that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PDAC liver metastasis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1465-7392eISSN: 1476-4679DOI: 10.1038/ncb3169Titel-ID: cdi_crossref_primary_10_1038_ncb3169
- Format
- –
- Schlagworte
- Animals, Base Sequence, Bone Marrow Cells - immunology, Carcinoma, Pancreatic Ductal - pathology, Cell Line, Tumor, Cell Movement, Exosomes - metabolism, Female, Fibronectins - biosynthesis, Gene Expression Regulation, Neoplastic, Hepatic Stellate Cells - pathology, Humans, Liver - cytology, Liver - pathology, Liver Neoplasms - genetics, Liver Neoplasms - pathology, Liver Neoplasms - secondary, Macrophage Migration-Inhibitory Factors - biosynthesis, Macrophages - immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Pancreatic Neoplasms - pathology, Precancerous Conditions - pathology, RNA Interference, RNA, Small Interfering, Sequence Analysis, RNA, Signal Transduction, Transforming Growth Factor beta - metabolism