PMID- 29641478
OWN - NLM
STAT- MEDLINE
DCOM- 20180907
LR  - 20181114
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 4
DP  - 2018 Apr 11
TI  - Conflicting Roles of Connexin43 in Tumor Invasion and Growth in the Central 
      Nervous System.
LID - 10.3390/ijms19041159 [doi]
LID - 1159
AB  - The tumor microenvironment is known to have increased levels of cytokines and 
      metabolites, such as glutamate, due to their release from the surrounding cells. 
      A normal cell around the tumor that responds to the inflammatory environment is 
      likely to be subsequently altered. We discuss how these abnormalities will 
      support tumor survival via the actions of gap junctions (GJs) and hemichannels 
      (HCs) which are composed of hexamer of connexin43 (Cx43) protein. In particular, 
      we discuss how GJ intercellular communication (GJIC) in glioma cells, the primary 
      brain tumor, is a regulatory factor and its attenuation leads to tumor invasion. 
      In contrast, the astrocytes, which are normal cells around the glioma, are 
      "hijacked" by tumor cells, either by receiving the transmission of malignant 
      substances from the cancer cells via GJIC, or perhaps via astrocytic HC activity 
      through the paracrine signaling which enable the delivery of these substances to 
      the distal astrocytes. This astrocytic signaling would promote tumor expansion in 
      the brain. In addition, brain metastasis from peripheral tissues has also been 
      known to be facilitated by GJs formed between cerebral vascular endothelial cells 
      and cancer cells. Astrocytes and microglia are generally thought to eliminate 
      cancer cells at the blood-brain barrier. In contrast, some reports suggest they 
      facilitate tumor progression as tumor cells take advantage of the normal 
      functions of astrocytes that support the survival of the neurons by exchanging 
      nutrients and metabolites. In summary, GJIC is essential for the normal 
      physiological function of growth and allowing the diffusion of physiological 
      substances. Therefore, whether GJIC is cancer promoting or suppressing may be 
      dependent on what permeates through GJs, when it is active, and to which cells. 
      The nature of GJs, which has been ambiguous in brain tumor progression, needs to 
      be revisited and understood together with new findings on Cx proteins and HC 
      activities.
FAU - Uzu, Miaki
AU  - Uzu M
AD  - Laboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of 
      Pharmaceutical Sciences, Chiba University, Chiba-shi, Chiba 263-8522, Japan. 
      muzu@ncc.go.jp.
AD  - Division of Cancer Pathophysiology, National Cancer Center Research Institute, 
      Chuo-ku, Tokyo 104-0045, Japan. muzu@ncc.go.jp.
FAU - Sin, Wun Chey
AU  - Sin WC
AD  - Department of Cellular and Physiological Sciences, Life Sciences Institute, 
      University of British Columbia, Vancouver, BC V6T 1Z3, Canada. wc.sin@ubc.ca.
FAU - Shimizu, Ayaka
AU  - Shimizu A
AD  - Laboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of 
      Pharmaceutical Sciences, Chiba University, Chiba-shi, Chiba 263-8522, Japan. 
      color.0v0.flower.182@gmail.com.
FAU - Sato, Hiromi
AU  - Sato H
AD  - Laboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of 
      Pharmaceutical Sciences, Chiba University, Chiba-shi, Chiba 263-8522, Japan. 
      hiromi-s@chiba-u.jp.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180411
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Connexin 43)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism/pathology
MH  - Blood-Brain Barrier/metabolism
MH  - Central Nervous System Neoplasms/*metabolism/pathology
MH  - Connexin 43/*metabolism
MH  - Gap Junctions/metabolism
MH  - Humans
MH  - Neoplasm Invasiveness
PMC - PMC5979343
OTO - NOTNLM
OT  - astrocyte
OT  - blood-brain barrier
OT  - central nervous system
OT  - connexin43
OT  - glioma
OT  - neurovascular unit
COIS- The authors declare no conflict of interest.
EDAT- 2018/04/12 06:00
MHDA- 2018/09/08 06:00
PMCR- 2018/04/01
CRDT- 2018/04/12 06:00
PHST- 2018/03/09 00:00 [received]
PHST- 2018/04/05 00:00 [revised]
PHST- 2018/04/09 00:00 [accepted]
PHST- 2018/04/12 06:00 [entrez]
PHST- 2018/04/12 06:00 [pubmed]
PHST- 2018/09/08 06:00 [medline]
PHST- 2018/04/01 00:00 [pmc-release]
AID - ijms19041159 [pii]
AID - ijms-19-01159 [pii]
AID - 10.3390/ijms19041159 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Apr 11;19(4):1159. doi: 10.3390/ijms19041159.