OBJECTIVETo investigate the expression of hepatocyte growth factor (HGF), and its receptor c-Met protein in nasopharyngeal carcinoma (NPC) and CNE-2 NPC cell line, to correlate their expression level with clinicopathologic features and to study the effect of HGF/c-Met system on the invasive and metastatic potential of NPC.

METHODSForty-five biopsies were collected from pre-treatment NPC patients during the period from 1999 to 2003. Immunohistochemical staining was used to detect the expression of HGF-alpha subunit and c-Met protein in NPC tissues. The association between expression of these proteins and clinicopathologic features was statistically analyzed. The expression of HGF and c-Met, as detected by flow cytometry, in CNE-2 NPC cell line (with or without exogenous HGF) was compared. Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) were also applied to evaluate the protein and mRNA expression of c-Met in CNE-2 cells.

RESULTSIn the 45 cases studied, the expression rate of c-Met was 91.1% (41/45). Only 1 case (2.2%, 1/45) showed positive signal for HGF in neoplastic cells. Instead, HGF was expressed in surrounding lymphocytes. The expression of c-Met positively correlated with lymph node metastasis (P = 0.024). There was also a positive correlation between expression of c-Met by tumor cells and expression of HGF by surrounding lymphocytes (r(s) = 0.450, P = 0.002). Moreover, the expression of c-Met was higher if there was a higher expression of HGF by lymphocytes (P = 0.009). However, there was no association between expression of c-Met and clinicopathologic features, such as age, gender, histopathologic type and clinical stage. After treatment with HGF for 24 hours, the percentage of c-Met-positive cells was significantly increased in CNE-2 cell line, from (46.6 +/- 9.02)% to (85.8 +/- 6.05)% (P = 0.003). The c-Met protein expression and c-Met mRNA level were also enhanced in CNE-2 cells with HGF treatment. However, endogenous HGF was not detected in CNE-2 cells, regardless of HGF treatment.

CONCLUSIONSHGF may play an important role in the development of NPC metastasis by inducing the expression of c-Met in tumor cells via a paracrine, instead of an autocrine, pathway.