[Functional aspects of protease-activated receptor 1 in promoting metastasis of lung cancer].
OBJECTIVE
To study the functional aspects of protease-activated receptor 1 (PAR-1) gene involved in tumor metastasis.


METHODS
Two human lung giant cell carcinoma cell lines PLA801C (low metastasis potential) and PLA801D (high metastasis potential) were chosen as in-vitro human cancer model systems. Sense and anti-sense expression constructs of PAR-1 gene (pC/PAR1s and pC/PAR1as) were transfected into PLA-801C and PLA-801D cells by lipofection. PAR-1 expression was determined by RT-PCR and western blot analysis. MTT growth, flow cytometry analysis, fibronectin adhesion, and matrigel invasion assays were used to study the effect of PAR-1 expression on the proliferation, adhesion, and invasion of the transfected cells.


RESULTS
Appropriate up-regulation or down-regulation of protein expression of PAR-1 was observed in both transfected cell lines (PLA801C and PLA801D) to express PAR-1s or PAR-1as, respectively. Expression of the sense PAR-1 markedly increased cellular proliferation, adhesion and invasion of PLA-801C cells. In contrast, anti-sense PAR-1 significantly inhibited cell growth, adhesion and invasion capabilities, along with cell arrest at G0/G1 phase of the PLA-801D cells.


CONCLUSIONS
Successful up- and down- regulation of expression of PAR-1 can be achieved by in-vitro transfection of sense and antisense PAR-1 constructs. PAR-1 may enhance metastasis of lung cancer through its regulation of cellular proliferation, adhesion and invasion. Down-regulation of expression of PAR-1 may provide a new therapeutic strategy against lung carcinoma.
Meng
Yu-hong
YH
Department of Pathology, Navy General Hospital of PLA, Beijing 100037, China.
Yu
Ji-yao
JY
Zhang
Jin-qiang
JQ
Lu
Ping
P
Ning
Hao-yong
HY
Hu
Ming
M
Lu
Ying-lin
YL
D018286:Carcinoma, Giant Cell / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016373:DNA, Antisense; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D016373:DNA, Antisense; D012333:RNA, Messenger; D044463:Receptor, PAR-1