Functional aspects of protease-activated receptor 1 in promoting metastasis of lung cancer.
- Author:
Yu-hong MENG
1
;
Ji-yao YU
;
Jin-qiang ZHANG
;
Ping LU
;
Hao-yong NING
;
Ming HU
;
Ying-lin LU
Author Information
- Publication Type:Journal Article
- MeSH: Carcinoma, Giant Cell; metabolism; pathology; Cell Adhesion; Cell Cycle; Cell Line, Tumor; Cell Proliferation; DNA, Antisense; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; metabolism; pathology; Neoplasm Invasiveness; RNA, Messenger; metabolism; Receptor, PAR-1; genetics; metabolism; Transfection
- From: Chinese Journal of Pathology 2007;36(5):313-317
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the functional aspects of protease-activated receptor 1 (PAR-1) gene involved in tumor metastasis.
METHODSTwo 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.
RESULTSAppropriate 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.
CONCLUSIONSSuccessful 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.