PMID- 20003523
OWN - NLM
STAT- MEDLINE
DCOM- 20100315
LR  - 20220223
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 9
DP  - 2009 Dec 15
TI  - ATP stimulates chemokine production via a store-operated calcium entry pathway in 
      C6 glioma cells.
PG  - 442
LID - 10.1186/1471-2407-9-442 [doi]
AB  - BACKGROUND: Glioma present as one of the most challenging cancers to treat, 
      however, understanding of tumor cell biology is not well understood. 
      Extracellular adenosine triphosphate (ATP) could serve as a critical signaling 
      molecule regulating tumor development. This study has examined pharmacological 
      modulation of calcium (Ca2+) entry through store-operated channels (SOC) on 
      cellular expression and production of immune-cell mobilizing chemokines in 
      ATP-stimulated C6 glioma cells. METHODS: Calcium spectrofluorometry was carried 
      out to measure mobilization of intracellular Ca2+ [Ca2+]i following ATP 
      stimulation of rat C6 glioma cells. Pretreatment with two inhibitors of SOC, 
      SKF96365 or gadolinium, was used to examine for effects on [Ca2+]i. RT-PCR was 
      performed to determine effects of purinergic stimulation on C6 cell expression of 
      metabotropic P2Y receptors (P2YR) and the chemokines, monocyte chemoattractant 
      protein-1 (MCP-1) and interleukin-8 (IL-8). ELISA was carried out to measure 
      production of MCP-1 and IL-8 with ATP stimulation of glioma cells. RESULTS: 
      Application of ATP (at 100 microM) to C6 glioma induced an increase in [Ca2+]i 
      with the response exhibiting two components of decay. In the presence of the SOC 
      inhibitors, SKF96365 or gadolinium, or with Ca2+-free solution, ATP responses 
      lacked a slow phase suggesting the secondary component was due to SOC-mediated 
      influx of Ca2+. RT-PCR confirmed expression of purinergic P2Y-subtype receptors 
      in C6 cells which would serve as a precursor to activation of SOC. In addition, 
      ATP-stimulated C6 cells showed enhanced expression of the chemokines, MCP-1 and 
      IL-8, with SKF96365 or gadolinium effective in reducing chemokine expression. 
      Gadolinium treatment of ATP-stimulated C6 cells was also found to inhibit the 
      production of MCP-1 and IL-8. CONCLUSION: These results suggest ATP-induced Ca2+ 
      entry, mediated by activation of SOC in C6 glioma, as a mechanism leading to 
      increased cellular expression and release of chemokines. Elevated levels of MCP-1 
      and IL-8 are predicted to enhance the mobility of tumor cells and promote 
      recruitment of microglia into developing tumors thereby supporting tumor growth.
FAU - Jantaratnotai, Nattinee
AU  - Jantaratnotai N
AD  - Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, 
      University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, V6T 
      1Z3, Canada. scnjt@mahidol.ac.th
FAU - Choi, Hyun B
AU  - Choi HB
FAU - McLarnon, James G
AU  - McLarnon JG
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091215
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Interleukin-8)
RN  - 0 (Receptors, Purinergic P2)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/*pharmacology
MH  - Animals
MH  - Calcium/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemokines/genetics/*metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Glioma/diagnosis/genetics/metabolism/*pathology
MH  - Interleukin-8/genetics/metabolism
MH  - Microglia/pathology
MH  - Neoplasm Invasiveness
MH  - Prognosis
MH  - Rats
MH  - Receptors, Purinergic P2/genetics/metabolism
MH  - Signal Transduction/drug effects/genetics
PMC - PMC2807438
EDAT- 2009/12/17 06:00
MHDA- 2010/03/17 06:00
PMCR- 2009/12/15
CRDT- 2009/12/17 06:00
PHST- 2009/07/07 00:00 [received]
PHST- 2009/12/15 00:00 [accepted]
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/03/17 06:00 [medline]
PHST- 2009/12/15 00:00 [pmc-release]
AID - 1471-2407-9-442 [pii]
AID - 10.1186/1471-2407-9-442 [doi]
PST - epublish
SO  - BMC Cancer. 2009 Dec 15;9:442. doi: 10.1186/1471-2407-9-442.