Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver

被引:2028
作者
Costa-Silva, Bruno [1 ,2 ]
Aiello, Nicole M. [3 ]
Ocean, Allyson J. [4 ]
Singh, Swarnima [1 ,2 ]
Zhang, Haiying [1 ,2 ]
Thakur, Basant Kumar [1 ,2 ,5 ]
Becker, Annette [1 ,2 ]
Hoshino, Ayuko [1 ,2 ]
Mark, Milica Tesic [6 ]
Molina, Henrik [6 ]
Xiang, Jenny [7 ]
Zhang, Tuo [7 ]
Theilen, Till-Martin [1 ,2 ]
Garcia-Santos, Guillermo [1 ,2 ]
Williams, Caitlin [1 ,2 ]
Ararso, Yonathan [1 ,2 ]
Huang, Yujie [1 ,2 ]
Rodrigues, Goncalo [1 ,2 ,8 ]
Shen, Tang-Long [9 ]
Labori, Knut Jorgen [10 ]
Lothe, Inger Marie Bowitz [11 ,12 ]
Kure, Elm H. [12 ]
Hernandez, Jonathan [13 ]
Doussot, Alexandre [13 ]
Ebbesen, Saya H. [1 ,2 ]
Grandgenett, Paul M. [14 ]
Hollingsworth, Michael A. [14 ]
Jain, Maneesh [15 ]
Mallya, Kavita [15 ]
Batra, Surinder K. [15 ]
Jarnagin, William R. [13 ]
Schwartz, Robert E. [16 ]
Matei, Irina [1 ,2 ]
Peinado, Hector [1 ,2 ,17 ]
Stanger, Ben Z. [3 ]
Bromberg, Jacqueline [18 ,19 ]
Lyden, David [1 ,2 ,20 ]
机构
[1] Weill Cornell Med Coll, Meyer Canc Ctr, Childrens Canc & Blood Fdn Labs, Drukier Inst Childrens Hlth,Dept Pediat, New York, NY 10021 USA
[2] Weill Cornell Med Coll, Meyer Canc Ctr, Childrens Canc & Blood Fdn Labs, Drukier Inst Childrens Hlth,Dept Cell & Dev Biol, New York, NY 10021 USA
[3] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Gastroenterol Div,Dept Med, Philadelphia, PA 19104 USA
[4] Weill Cornell Med Coll, New York Presbyterian Hosp, Div Hematol & Med Oncol, Dept Med, New York, NY 10021 USA
[5] Hannover Med Sch, Dept Pediat Hematol & Oncol, D-30625 Hannover, Germany
[6] Rockefeller Univ, Prote Resource Ctr, New York, NY 10065 USA
[7] Weill Cornell Med Coll, Genom Resources Core Facil, New York, NY 10021 USA
[8] Univ Porto, Abel Salazar Biomed Sci Inst, Grad Program Areas Basic & Appl Biol, P-4099003 Oporto, Portugal
[9] Natl Taiwan Univ, Dept Plant Pathol & Microbiol, Taipei 10617, Taiwan
[10] Oslo Univ Hosp, Dept Hepatopancreatobiliary Surg, N-0424 Oslo, Norway
[11] Oslo Univ Hosp, Dept Pathol, N-0424 Oslo, Norway
[12] Oslo Univ Hosp, Dept Genet, Inst Canc Res, N-0424 Oslo, Norway
[13] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA
[14] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA
[15] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
[16] Weill Cornell Med Coll, Dept Med, Div Gastroenterol & Hepatol, New York, NY 10021 USA
[17] Spanish Natl Canc Res Ctr CNIO, Dept Mol Oncol, Microenvironm & Metaslasis Lab, Madrid 28029, Spain
[18] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA
[19] Weill Cornell Med Coll, New York, NY 10065 USA
[20] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA
关键词
GROWTH-FACTOR-BETA; INHIBITORY FACTOR EXPRESSION; TGF-BETA; MESENCHYMAL TRANSITION; EXTRACELLULAR VESICLES; DUCTAL ADENOCARCINOMA; KUPFFER CELLS; MOUSE MODEL; MACROPHAGES; ACTIVATION;
D O I
10.1038/ncb3169
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 beta 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.
引用
收藏
页码:816 / +
页数:20
相关论文
共 69 条
  • [61] 2-J
  • [62] Control of Tumor-Associated Macrophage Alternative Activation by Macrophage Migration Inhibitory Factor
    Yaddanapudi, Kavitha
    Putty, Kalyani
    Rendon, Beatriz E.
    Lamont, Gwyneth J.
    Faughn, Jonathan D.
    Satoskar, Abhay
    Lasnik, Amanda
    Eaton, John W.
    Mitchell, Robert A.
    [J]. JOURNAL OF IMMUNOLOGY, 2013, 190 (06) : 2984 - 2993
  • [63] TSU68 Prevents Liver Metastasis of Colon Cancer Xenografts by Modulating the Premetastatic Niche
    Yamamoto, Masayoshi
    Kikuchi, Hirotoshi
    Ohta, Manabu
    Kawabata, Toshiki
    Hiramatsu, Yoshihiro
    Kondo, Kenji
    Baba, Megumi
    Kamiya, Kinji
    Tanaka, Tatsuo
    Kitagawa, Masatoshi
    Konno, Hiroyuki
    [J]. CANCER RESEARCH, 2008, 68 (23) : 9754 - 9762
  • [64] Macrophage migration inhibitory factor expression correlates with inflammatory changes in human chronic hepatitis B infection
    Zhang, HY
    Nanji, AA
    Luk, JM
    Huang, XR
    Lo, CM
    Chen, YX
    Yuen, ST
    Lan, HY
    Lau, GKK
    [J]. LIVER INTERNATIONAL, 2005, 25 (03) : 571 - 579
  • [65] Development and characterization of a reliable mouse model of colorectal cancer metastasis to the liver
    Zhang, Yu
    Davis, Celestia
    Ryan, James
    Janney, Cory
    Pena, Maria Marjorette O.
    [J]. CLINICAL & EXPERIMENTAL METASTASIS, 2013, 30 (07) : 903 - 918
  • [66] Zhong Silin, 2011, Cold Spring Harb Protoc, V2011, P940, DOI 10.1101/pdb.prot5652
  • [67] Zoller Margot, 2013, World J Gastrointest Pathophysiol, V4, P74, DOI 10.4291/wjgp.v4.i4.74
  • [68] Zvibel I, 1998, INT J CANCER, V77, P295, DOI 10.1002/(SICI)1097-0215(19980717)77:2<295::AID-IJC20>3.0.CO
  • [69] 2-9