[PAR-1 regulation of intracellular Ca²(+) mobilization in pulmonary giant cell carcinoma cell line PLA801D/PLA801C].
OBJECTIVE
To investigate molecular mechanisms of PAR-1 regulation on intracellular Ca²(+) mobilization in lung giant cell carcinoma cells in vitro and its involvement in tumor metastasis.


METHODS
Free intracellular Ca²(+) ([Ca²(+)]i) was measured in lung giant cell carcinoma PLA801C and PLA801D cells by confocal microscopy. Sense and anti-sense PAR-1 expression vectors were transfected into PLA801C (C+)and PLA801D(D-) cells, respectively. The effects of PAR-1 expression were investigated by thrombin and TRAP-induced mobilization of [Ca²(+)]i in the C+ and D-cells.


RESULTS
There were significant differences of the mean values of [Ca²(+)]i between PLA801D (59.55) and PLA801C cells (35.46, P < 0.01). The mean [Ca²(+)]i of C+ cells (45.77) was significantly higher than that of its control CV cells (35.46, P < 0.05), and the mean [Ca²(+)]i of D-cells (48.42) was significantly lower than that of its control DV cells (59.55, P < 0.05). The peaks of [Ca²(+)]i of C+ and CV cells were 48.19 ± 9.84 and 45.64 ± 9.87 (P < 0.05) respectively at 80 s and 100 s after thrombin treatment, but were 111.31 ± 25.00 and 52.93 ± 11.21 (P < 0.05) respectively at 60 s after TRAP treatment. The peaks of [Ca²(+)]i of D- and DV cells were 40.71 ± 5.89 and 61.07 ± 21.36 (P < 0.05) respectively at 60 s after thrombin treatment, but were 84.98 ± 11.23 and 102.58 ± 21.48 (P < 0.05) respectively at 40 s after TRAP treatment.


CONCLUSIONS
The high metastatic potential of PLA801D and PLA801C may be related to [Ca²(+)]i of the tumor cells. PAR-1 may play an important role in the metastasis of lung giant cell carcinoma cells by up-regulating the intracellular Ca²(+).
Meng
Yu-hong
YH
Department of Pathology, Navy General Hospital of PLA, Beijing, China. bjmengyh@yahoo.com.cn
Zhang
Jin-qiang
JQ
Ning
Hao-yong
HY
Lu
Ping
P
Hong
Liu
L
Liu
Xiao
X
Kang
Xiao-ling
XL
Yu
Ji-yao
JY
Lu
Ying-lin
YL
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D018286:Carcinoma, Giant Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D016373:DNA, Antisense / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018179:Receptors, Thrombin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D014162:Transfection; D015854:Up-Regulation
D016373:DNA, Antisense; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D013917:Thrombin; D002118:Calcium