PMID- 30734278
OWN - NLM
STAT- Publisher
LR  - 20190221
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
DP  - 2019 Feb 8
TI  - Colorectal cancer exosomes induce lymphatic network remodeling in lymph nodes.
LID - 10.1002/ijc.32196 [doi]
AB  - The lymphatic network remodeling may guide tumor metastasis in a sentinel lymph
      node (SLN). Although tumor-derived exosomes have been demonstrated to modify the 
      microenvironment in adjacent organs and initiate a premetastatic niche, their
      influence on the lymphatic network in SLNs has not been explained. Here, we show 
      that CT26 cell exosomes (Exo) promote the proliferation of lymphatic endothelial 
      cells and the formation of lymphatic network in SLN, facilitating the SLN
      metastasis of colorectal cancer (CRC). Uptake of Exo by macrophages promoted
      VEGFC secretion both in vivo and in vitro. Exo increased the frequency of
      F4/80(+) macrophages in the SLN. Macrophage ablation by clodrosome prevented the 
      exosomal effect on lymphatic network remodeling and SLN metastasis. Exosomal
      IRF-2 was highly expressed in serum exosomes isolated from CRC patients with LN
      metastasis relative to patients without LN metastasis and healthy controls.
      Mechanistically, exosomal IRF-2 induced the release of VEGFC by macrophages. An
      IRF-2 knockdown attenuated the lymphatic network remodeling in the SLN and
      suppressed the SLN metastasis. Our data suggest that exosomal IRF-2 remodels the 
      lymphatic network in an SLN and may predict the development of CRC LN metastases.
CI  - (c) 2019 UICC.
FAU - Sun, Bo
AU  - Sun B
AD  - Department of Gastric Cancer, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of General Surgery, Huashan Hospital, Fudan University, Shanghai,
      China.
FAU - Zhou, Yiming
AU  - Zhou Y
AD  - Department of General Surgery, Huashan Hospital, Fudan University, Shanghai,
      China.
FAU - Fang, Yantian
AU  - Fang Y
AD  - Department of Gastric Cancer, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
FAU - Li, Zhenyang
AU  - Li Z
AD  - Department of General Surgery, Huashan Hospital, Fudan University, Shanghai,
      China.
FAU - Gu, Xiaodong
AU  - Gu X
AD  - Department of General Surgery, Huashan Hospital, Fudan University, Shanghai,
      China.
FAU - Xiang, Jianbin
AU  - Xiang J
AUID- ORCID: https://orcid.org/0000-0001-7208-2023
AD  - Department of General Surgery, Huashan Hospital, Fudan University, Shanghai,
      China.
LA  - eng
GR  - No.17410742100/"Belt and Road" Young Scientist Communication International
      Cooperation Project
GR  - No. 81201618/National Natural Science Foundation of China
PT  - Journal Article
DEP - 20190208
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
OTO - NOTNLM
OT  - IRF-2
OT  - colorectal cancer
OT  - exosome
OT  - lymphangiogenesis
EDAT- 2019/02/09 06:00
MHDA- 2019/02/09 06:00
CRDT- 2019/02/09 06:00
PHST- 2017/11/06 00:00 [received]
PHST- 2019/01/26 00:00 [revised]
PHST- 2019/01/31 00:00 [accepted]
PHST- 2019/02/09 06:00 [pubmed]
PHST- 2019/02/09 06:00 [medline]
PHST- 2019/02/09 06:00 [entrez]
AID - 10.1002/ijc.32196 [doi]
PST - aheadofprint
SO  - Int J Cancer. 2019 Feb 8. doi: 10.1002/ijc.32196.