| Objective: This study was conducted to detect the expression of hepatocyte growth factor(HGF) and its receptor(c-Met), E-cadherin and β -catenin proteins in non-small cell lung carcinoma(NSCLC), to explore their expression relationship with clinic pathological parameters, to investigate the relationship among four proteins. Meanwhile, to explore the effects of proliferation, adhesion, mobility and invasion in lung adenocarcinoma cell line A549 by exogenous HGF. To investigate the regulation of the expression of c-Met, E-cadherin and β-catenin in A549 cell line by HGF. Our study was to reveal the effects and mechanisms of HGF, c-Met on invasion and metastasis of NSCLC.Methods: Immunohistochemistry(S-P method) was adopted to detect the HGF, c-Met, E-cadherin and β -catenin proteins expression in 45 NSCLC. Human lung adenocarcinoma A549 cell line was cultivated, cell line was divided into four groups(0ng/ml, 20ng/ml, 40ng/ml, 80ng/ml) according to the concentrations of exogenous HGF-human recombinant HGF(rhHGF). In control group rhHGF was not used, the rest were experiment groups. MTT method was used to detect the difference of proliferation and adhesion in four groups. Trans-well invasion model was used to detect the difference of mobility and invasion capability in four groups. Immunocytochemistry was used to detect the alteration of c-Met, E-cadherin and β -catenin proteins expression in A549 cell by additional HGF.Results: (l)In 45 NSCLC, positive rates of HGF and c-Met proteins were 51.1%(23/45), 60.0%(27/45) respectively. (2)HGF expression was correlated with lymph node metastasis (P<0.05). c-Met expression was related to higher differentiation degree and histotype(P < 0.05). (3)There was positive relationship between the expressions of HGF and c-Met (P<0.05, r=0.472) in NSCLC. 19 of 45 NSCLC (42.2%) were found to co-express HGF and c-Met, 13 of 19 (68.4%) were autocrine, 6 of 19 (31.6%) were paracrine. (4) Abnormal expression rates of E-cadherin and β -catenin proteins were 71.1%(32/45), 77.8%(35/45) respectively. (5)Abnormalexpression of E-cadherin proteins and ￡ -catenin proteins was both correlated with lymph node metastasis (P<0.05). (6)Statiscal relation was observed between abnormal expression of 3 -catenin protein and abnormal E-cadherin expression and c-Met expression respectively(ra=0.367, i>i<0.05; r2=0.436, F2<0.05). (7)Compared with control group, rhHGF promoted A549 cell line growth and adhesion, the difference was significant(P<0.01). (8)The migration and invasion capability of A549 cell line was significantly increased after treated with rhHGF(P<0.01). (9)Stimulation by rhHGF, E-cadherin expression was decreased, 3 -catenin proteins was located from cell membrane to cell cytoplasm.Conclusion: (1) HGF and c-Met have high level expression in NSCLC, both are involved in invasion and metastasis of NSCLC by autocrine and paracrine. (2) It is a common event of the abnormal expression of E-cadherin and P -catenin. The anomalous expression of E-cadherin and ￡ -catenin lead to reduce cell-cell homotypic adhesion, thus play an important role in infiltration and metastasis of NSCLC. (3) Abnormal expression of P -catenin protein is correlated with the expression of c-Met in NSCLC tissue. (4) HGF can promote proliferation, adhesion, mobility and invasion of NSCLC cell (A549 cell line) in vitro. (5) E-cadherin expression is decreased, P -catenin proteins is translocated from cell membrane to cell cytoplasm by exogenous HGF in NSCLC cell. (6)HGF and c-Met is involved in progression and development of NSCLC by autocrine and paracrine. HGF induces the alteration of expression of ￡ -catenin and E-cadherin proteins in the process. |
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