Tumour exosome integrins determine organotropic metastasis
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Tumour exosome integrins determine organotropic metastasis. / Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Jørgen Labori, Knut; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David.
In: NATURE, Vol. 527, No. 7578, 19.11.2015, p. 329-35.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Tumour exosome integrins determine organotropic metastasis
AU - Hoshino, Ayuko
AU - Costa-Silva, Bruno
AU - Shen, Tang-Long
AU - Rodrigues, Goncalo
AU - Hashimoto, Ayako
AU - Tesic Mark, Milica
AU - Molina, Henrik
AU - Kohsaka, Shinji
AU - Di Giannatale, Angela
AU - Ceder, Sophia
AU - Singh, Swarnima
AU - Williams, Caitlin
AU - Soplop, Nadine
AU - Uryu, Kunihiro
AU - Pharmer, Lindsay
AU - King, Tari
AU - Bojmar, Linda
AU - Davies, Alexander E
AU - Ararso, Yonathan
AU - Zhang, Tuo
AU - Zhang, Haiying
AU - Hernandez, Jonathan
AU - Weiss, Joshua M
AU - Dumont-Cole, Vanessa D
AU - Kramer, Kimberly
AU - Wexler, Leonard H
AU - Narendran, Aru
AU - Schwartz, Gary K
AU - Healey, John H
AU - Sandstrom, Per
AU - Jørgen Labori, Knut
AU - Kure, Elin H
AU - Grandgenett, Paul M
AU - Hollingsworth, Michael A
AU - de Sousa, Maria
AU - Kaur, Sukhwinder
AU - Jain, Maneesh
AU - Mallya, Kavita
AU - Batra, Surinder K
AU - Jarnagin, William R
AU - Brady, Mary S
AU - Fodstad, Oystein
AU - Muller, Volkmar
AU - Pantel, Klaus
AU - Minn, Andy J
AU - Bissell, Mina J
AU - Garcia, Benjamin A
AU - Kang, Yibin
AU - Rajasekhar, Vinagolu K
AU - Ghajar, Cyrus M
AU - Matei, Irina
AU - Peinado, Hector
AU - Bromberg, Jacqueline
AU - Lyden, David
PY - 2015/11/19
Y1 - 2015/11/19
N2 - Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate 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. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
AB - Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate 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. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
U2 - 10.1038/nature15756
DO - 10.1038/nature15756
M3 - SCORING: Journal article
C2 - 26524530
VL - 527
SP - 329
EP - 335
JO - NATURE
JF - NATURE
SN - 0028-0836
IS - 7578
ER -