PMID- 28416823
OWN - NLM
STAT- MEDLINE
DCOM- 20180629
LR  - 20190816
IS  - 1671-167X (Print)
IS  - 1671-167X (Linking)
VI  - 49
IP  - 2
DP  - 2017 Apr 18
TI  - [Identification of a new pro-invasion factor in tumor microenvironment: progress 
      in function and mechanism of extracellular ATP].
PG  - 188-195
AB  - Up to 90% of all cancer related morbidity and mortality can be attributed to 
      metastasis. In recent years the study of tumor microenvironment, its cellular and 
      molecular components, and how they can affect neoplastic progression toward 
      metastasis, has become a hot focus in cancer research. Accumulated evidence shows 
      that the formation of metastasis is a multi-step sequential process, in which, 
      the tumor cells continuously interact with the host microenvironment. Host 
      derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines, 
      etc. together with different types of host cells, play important roles in the 
      tumor progression towards metastasis. The interaction between the tumor cells and 
      host microenvironment determines the fate of metastasis. The reveal of this 
      interaction mechanism provides us an opportunity to find effective mode of 
      interference and develop novel anti-metastasis drugs. In this review, we have 
      summarized our work on a new pro-invasion factor identified in tumor 
      microenvironment and how it affects tumor invasion and metastass. Adenosine 
      triphosphate (ATP), the key intracellular energy currency, accumulates within the 
      tumor microenvironment and is closely involved in cancer cell metabolism and in 
      antitumor immunity. The established role of ATP as a growth modulator and a 
      proinflammatory mediator endues ATP and other purines with potential players in 
      host-tumor interaction. Our study demonstrated that extracellular ATP stimulated 
      human cancer invasion in in vitro tests. Increased migration and invasive ability 
      across Matrigel was observed in some human carcinoma cell lines, including the 
      prostate, breast, colon, melanoma and lung, when stimulated with ATP or its 
      analogues. ATP enhanced the motility of cancer cells via increasing the amount 
      and length of lamellipodia and filopodia, which were necessary for the cell 
      motility. Significant increase in Rac1 and Cdc42 activities was observed. Using 
      cDNA microarray we found that the expression of a panel of 
      invasion/metastasis-related genes was significantly changed, including the 
      increased expression of interleukin (IL)-8 and matrix metalloproteinase-3 (MMP-3) 
      after ATP treatment. Changes of some epithelial-mesenchymal transition 
      (EMT)-related factors were also observed, including the increase of snail, 
      decrease of E-cadherin and claudin-1. Multiple P2Y receptors subtypes were 
      expressed on tumor cells, but P2Y2 and P2X7 receptors were found to be mainly 
      responsible for the pro-invasive effect of ATP. Down-regulation of either P2Y2 or 
      P2X7 abolished ATP effect on cancer invasion and expression of 
      EMT/invasion-related genes. Further, we found that P2Y2 receptor trans-activated 
      with epidermal growth factor receptor (EGFR) and co-activated extracellular 
      regulated protein kinases (ERK1/2) signaling pathway, which was involved in 
      regulating expression of EMT and other related genes. In nude mice experiment, 
      the pro-invasive effect of ATP was further confirmed. In summary, our results 
      reveal that ATP is a potential pro-invasive factor in tumor microenvironment. 
      P2Y2/P2X7 receptors act as a mediator in the regulation of ATP-induced EMT and 
      invasion of cancer cells. Given that tumor microenvironment is rich in ATP and 
      other purines, we hypothesize that ATP might be a potential invasion stimulator 
      in tumor microenvironment. Blocking ATP receptor might be a therapeutic target on 
      cancer.
FAU - Fang, W G
AU  - Fang WG
AD  - Department of Pathology, Peking University School of Basic Medical Sciences, 
      Beijing 100191, China.
FAU - Tian, X X
AU  - Tian XX
AD  - Department of Pathology, Peking University School of Basic Medical Sciences, 
      Beijing 100191, China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Beijing Da Xue Xue Bao Yi Xue Ban
JT  - Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health 
      sciences
JID - 101125284
RN  - 0 (Antigens, CD)
RN  - 0 (CDH1 protein, human)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Interleukin-8)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Adenosine Triphosphate/*physiology
MH  - Animals
MH  - Antigens, CD
MH  - Cadherins/physiology
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Epithelial-Mesenchymal Transition
MH  - ErbB Receptors/physiology
MH  - Humans
MH  - Interleukin-8
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Neoplasm Invasiveness
MH  - Prostate
MH  - Receptors, Purinergic P2Y2
MH  - *Signal Transduction
MH  - *Tumor Microenvironment
EDAT- 2017/04/19 06:00
MHDA- 2018/06/30 06:00
CRDT- 2017/04/19 06:00
PHST- 2017/04/19 06:00 [entrez]
PHST- 2017/04/19 06:00 [pubmed]
PHST- 2018/06/30 06:00 [medline]
PST - ppublish
SO  - Beijing Da Xue Xue Bao Yi Xue Ban. 2017 Apr 18;49(2):188-195.