摘要
目的 探讨肝细胞生长因子(HGF)及其受体c- Met蛋白在鼻咽癌组织中的表达水平,研究HGF/c- Met系统对鼻咽癌细胞侵袭转移的影响。方法 收集1999—2003年期间45例确诊的鼻咽原发癌活检组织标本,采用免疫组织化学(LSAB)法检测鼻咽癌组织中HGF α亚单位和c- Met的表达,并与患者的病理及临床资料相联系。采用流式细胞术检测鼻咽癌细胞株CNE- 2在HGF刺激前后c- Met阳性癌细胞百分率的改变;蛋白印迹法和逆转录PCR法分别用于检测癌细胞株c -Met蛋白表达和mRNA表达的变化。结果 在45例鼻咽原发癌组织中,癌细胞c- Met的阳性表达率为91. 1% (41 /45),但仅有1例鼻咽癌细胞表达HGF( 2 .2%, 1 /45 )。HGF主要在鼻咽癌间质中的淋巴细胞表达。癌细胞c Met的表达水平与淋巴结转移有关(P=0 .024 ),且与淋巴细胞表达HGF呈正相关(rs=0 .450,P=0 .002)。癌细胞c Met表达量在间质淋巴细胞高表达HGF的病例中明显高于淋巴细胞低表达HGF的癌组织(P=0 .009)。但癌细胞c Met的表达与患者性别、年龄、病理组织学分型以及临床分期均未显示相关性。鼻咽癌细胞株CNE 2在HGF诱导24h后,c Met阳性的癌细胞比例即有明显增加,由(46 .6±9 .02)%增加至(85. 8±6. 05)% (P=0 .003 ),癌细胞c Met蛋白表达相对强度和mRNA表达水平均有显著提高,?
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-α 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.
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2005年第2期75-79,共5页
Chinese Journal of Pathology
基金
国家自然科学基金资助项目(30200254)
广东省自然科学基金资助项目(031672)
