PMID- 37263461
OWN - NLM
STAT- MEDLINE
DCOM- 20230728
LR  - 20230729
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 109
DP  - 2023 Sep
TI  - Exosomal B7-H3 facilitates colorectal cancer angiogenesis and metastasis through 
      AKT1/mTOR/VEGFA pathway.
PG  - 110737
LID - S0898-6568(23)00151-1 [pii]
LID - 10.1016/j.cellsig.2023.110737 [doi]
AB  - B7-H3 (CD276), an immune checkpoint molecule, is aberrantly overexpressed in many 
      types of cancer, and plays important roles in tumor immune evasion, 
      carcinogenesis and metastasis, as well as angiogenesis. However, the mechanisms 
      underlying B7-H3-promoted angiogenesis are still largely unknown. In this study, 
      based on the observation of overexpression of B7-H3 on the tumor cells and 
      vascular endothelial cells (VECs) in colorectal cancer (CRC) tissues, we 
      investigated the roles of cancer cell-drived exosomal B7-H3 in tumor angiogenesis 
      and metastasis through crosstalk between cancer cells and VECs. We found that CRC 
      cell-drived exosomal B7-H3 was uptaken by human umbilical vein endothelial cells 
      (HUVECs) and consequently activated the AKT serine/threonine kinase 1 (AKT1) / 
      mechanistic target of rapamycin kinase (mTOR) / vascular endothelial growth 
      factor A (VEGFA) signaling pathway, thus augmenting the abilities of migration, 
      invasion and tube formation of HUVECs. Furthermore, administration of CRC 
      cell-drived exosomes with reinforced B7-H3 promoted the pulmonary angiogenesis 
      and metastasis of CRC cells in mice. In addition, high expression of B7-H3 was 
      observed in urinary exosomes isolated from CRC patients. Our findings reveal that 
      CRC-derived exosomal B7-H3 promotes tumor angiogenesis and metastasis by 
      activating the AKT1/mTOR/VEGFA signaling pathway. It provides novel insights into 
      the roles of CRC-drived exosomes in CRC progression.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Wu, Rendi
AU  - Wu R
AD  - Department of oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 
      Province 214122, China; Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu Province 214122, China.
FAU - Zhang, Yawen
AU  - Zhang Y
AD  - College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu Province 
      215123, China.
FAU - Xu, Xinyi
AU  - Xu X
AD  - Department of oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 
      Province 214122, China.
FAU - You, Qingjun
AU  - You Q
AD  - Department of Thoracic Surgery, The Affiliated Hospital of Jiangnan University, 
      Wuxi, Jiangsu Province 214062, China.
FAU - Yu, Chunjing
AU  - Yu C
AD  - Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, Wuxi, 
      Jiangsu Province, 214062, China.
FAU - Wang, Weipeng
AU  - Wang W
AD  - College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu Province 
      215123, China. Electronic address: wangweipeng@suda.edu.cn.
FAU - Mao, Yong
AU  - Mao Y
AD  - Department of oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 
      Province 214122, China; Wuxi School of Medicine, Jiangnan University, Wuxi, 
      Jiangsu Province 214122, China. Electronic address: 9812015252@jiangnan.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230530
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (VEGFA protein, human)
RN  - 0 (CD276 protein, human)
RN  - 0 (B7 Antigens)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - *Colorectal Neoplasms/pathology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - Neovascularization, Pathologic/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - *MicroRNAs/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - B7 Antigens/metabolism
OTO - NOTNLM
OT  - Angiogenesis
OT  - B7-H3
OT  - Colorectal cancer
OT  - Exosome
OT  - Metastasis
COIS- Declaration of Competing Interest The authors declare no conflicts of interest.
EDAT- 2023/06/02 01:07
MHDA- 2023/07/28 06:42
CRDT- 2023/06/01 19:25
PHST- 2023/01/01 00:00 [received]
PHST- 2023/04/24 00:00 [revised]
PHST- 2023/05/26 00:00 [accepted]
PHST- 2023/07/28 06:42 [medline]
PHST- 2023/06/02 01:07 [pubmed]
PHST- 2023/06/01 19:25 [entrez]
AID - S0898-6568(23)00151-1 [pii]
AID - 10.1016/j.cellsig.2023.110737 [doi]
PST - ppublish
SO  - Cell Signal. 2023 Sep;109:110737. doi: 10.1016/j.cellsig.2023.110737. Epub 2023 
      May 30.