Exosomes released from pancreatic cancer cells enhance angiogenic activities via dynamin-dependent endocytosis in endothelial cells in vitro

被引:67
作者
Chiba, Mitsuru [1 ]
Kubota, Shiori [2 ]
Sato, Konomi [2 ]
Monzen, Satoru [3 ]
机构
[1] Hirosaki Univ, Grad Sch Hlth Sci, Dept Biosci & Lab Med, 66-1 Hon Cho, Hirosaki, Aomori 0368564, Japan
[2] Hirosaki Univ, Dept Med Technol, Sch Hlth Sci, 66-1 Hon Cho, Hirosaki, Aomori 0368564, Japan
[3] Hirosaki Univ, Grad Sch Hlth Sci, Dept Radiat Sci, 66-1 Hon Cho, Hirosaki, Aomori 0368564, Japan
关键词
MICROVESICLES; INHIBITION; ACTIVATION; TRIGGERS; RECEPTOR; INDUCE; VEGF;
D O I
10.1038/s41598-018-30446-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pancreatic cancer has the lowest 5 year survival rate among all cancers. Several extracellular factors are involved in the development and metastasis of pancreatic cancer to distant organs. Exosomes are lipid-bilayer, membrane-enclosed nanoparticles that are recognised as important mediators of cell-to-cell communications. However, the role of exosomes released from pancreatic cancer cells in tumour micro-environment remains unknown. Here, we show that exosomes released from pancreatic cancer PK-45H cells activate various gene expressions in human umbilical vein endothelial cells (HUVECs) by in vitro analyses. In addition, these exosomes released from PK-45H cells promote phosphorylation of Akt and ERK1/2 signalling pathway molecules and tube formation via dynamin-dependent endocytosis in HUVECs. Our findings suggested that exosomes released from pancreatic cancer cells may act as a novel angiogenesis promoter.
引用
收藏
页数:9
相关论文
共 36 条
[1]   Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis [J].
Bergers, G ;
Brekken, R ;
McMahon, G ;
Vu, TH ;
Itoh, T ;
Tamaki, K ;
Tanzawa, K ;
Thorpe, P ;
Itohara, S ;
Werb, Z ;
Hanahan, D .
NATURE CELL BIOLOGY, 2000, 2 (10) :737-744
[2]   VEGF as a key mediator of angiogenesis in cancer [J].
Carmeliet, P .
ONCOLOGY, 2005, 69 :4-10
[3]   Exosomes derived from SW480 colorectal cancer cells promote cell migration in HepG2 hepatocellular cancer cells via the mitogen-activated protein kinase pathway [J].
Chiba, Mitsuru ;
Watanabe, Narumi ;
Watanabe, Miki ;
Sakamoto, Maki ;
Sato, Akika ;
Fujisaki, Mizuki ;
Kubota, Shiori ;
Monzen, Satoru ;
Maruyama, Atsushi ;
Nanashima, Naoki ;
Kashiwakura, Ikuo ;
Nakamura, Toshiya .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2016, 48 (01) :305-312
[4]   Exosomes secreted from human colorectal cancer cell lines contain mRNAs, microRNAs and natural antisense RNAs, that can transfer into the human hepatoma HepG2 and lung cancer A549 cell lines [J].
Chiba, Mitsuru ;
Kimura, Misako ;
Asari, Saya .
ONCOLOGY REPORTS, 2012, 28 (05) :1551-1558
[5]   Sulforaphane inhibits angiogenesis through activation of FOXO transcription factors [J].
Davis, Rachel ;
Singh, Karan P. ;
Kurzrock, Razelle ;
Shankar, Sharmila .
ONCOLOGY REPORTS, 2009, 22 (06) :1473-1478
[6]  
DeSilva DR, 1998, J IMMUNOL, V160, P4175
[7]   Cellular and molecular aspects of pancreatic cancer [J].
Gharibi, A. ;
Adamian, Y. ;
Kelber, J. A. .
ACTA HISTOCHEMICA, 2016, 118 (03) :305-316
[8]   Microvesicles Released from Human Renal Cancer Stem Cells Stimulate Angiogenesis and Formation of Lung Premetastatic Niche [J].
Grange, Cristina ;
Tapparo, Marta ;
Collino, Federica ;
Vitillo, Loriana ;
Damasco, Christian ;
Deregibus, Maria Chiara ;
Tetta, Ciro ;
Bussolati, Benedetta ;
Camussi, Giovanni .
CANCER RESEARCH, 2011, 71 (15) :5346-5356
[9]   Cancer metastases: challenges and opportunities [J].
Guan, Xiangming .
ACTA PHARMACEUTICA SINICA B, 2015, 5 (05) :402-418
[10]   Paracrine induction of endothelium by tumor exosomes [J].
Hood, Joshua L. ;
Pan, Hua ;
Lanza, Gregory M. ;
Wickline, Samuel A. .
LABORATORY INVESTIGATION, 2009, 89 (11) :1317-1328