[Expression of hepatocyte growth factor/c-Met system in nasopharyngeal carcinoma and its biological significance].
OBJECTIVE
To 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.


METHODS
Forty-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.


RESULTS
In 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.


CONCLUSIONS
HGF 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.
Li
Zhi
Z
Department of Pathology, Sun Yat-sen Medical College, Sun Yat-sen University, Guangzhou 510089, China. pathol@gzsums.edu.cn
Lin
Su-Xia
SX
Liang
Hui-Zhen
HZ
He
Jie-Hua
JH
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D008207:Lymphatic Metastasis; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met