Sheu Lai-Fa, Lee Wen-Cheng, Lee Herng-Sheng, Kao Woei-Yau, Chen Ann
Department of Pathology, National Defence Medical Centre, Taipei, Taiwan, Republic of China.
J Pathol. 2005 Oct;207(2):216-23. doi: 10.1002/path.1822.
Expression of c-kit has been demonstrated in 33% of adult nasopharyngeal carcinomas (NPCs) and in 88% of paediatric NPCs. Patients with tumours expressing c-kit tend to exhibit better survival, but a paracrine/autocrine function for the stem cell factor (SCF)/c-kit system in nasopharyngeal carcinomas has not been reported. This study evaluated the expression of c-kit and SCF by immunohistochemical staining of nasopharyngeal epithelium (NPE) and of primary and metastatic NPCs. In addition, c-kit and SCF expression were studied in HONE-1 NPC cells by immunoprecipitation and western blotting. Expression of c-kit and SCF was detected in 75% and 57% of NPE, respectively, and there was 48% co-expression. In primary NPCs, 86% expressed c-kit, 69% had SCF expression, and there was 67% co-expression. In metastatic NPCs, 76% expressed c-kit, 72% expressed SCF and there was 68% co-expression. Co-expression of c-kit and SCF with tyrosine autophosphorylation of p145(c - kit) was demonstrated in HONE-1 NPC cells. In addition, the expression level of c-kit and its autophosphorylation status was not obviously influenced by the transient co-expression of Epstein-Barr nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1). Co-expression of c-kit and SCF is therefore commonly found in nasopharyngeal epithelium and NPCs, and in HONE-1 NPC cells with autoactivation possibly independent of the co-expression of EBNA1 and LMP1. All of these findings suggest that autoactivation of SCF/c-kit signalling may be a potent regulator of the nasopharyngeal epithelial barrier and of immune function at the nasopharyngeal mucosa surface, and may contribute to the carcinogenesis and progression of NPC. Further molecular analysis is required to evaluate the possibility of treatment with tyrosine kinase inhibitors in NPC, analogous to the treatment of gastrointestinal stromal tumours with STI571.
已证实33%的成人鼻咽癌（NPC）和88%的儿童NPC中存在c-kit表达。肿瘤表达c-kit的患者往往具有更好的生存率，但尚未见有关鼻咽癌中干细胞因子（SCF）/c-kit系统旁分泌/自分泌功能的报道。本研究通过对鼻咽上皮（NPE）、原发性和转移性NPC进行免疫组织化学染色来评估c-kit和SCF的表达。此外，通过免疫沉淀和蛋白质印迹法研究了HONE-1 NPC细胞中c-kit和SCF的表达。分别在75%的NPE和57%的NPE中检测到c-kit和SCF的表达，共表达率为48%。在原发性NPC中，86%表达c-kit，69%有SCF表达，共表达率为67%。在转移性NPC中，76%表达c-kit，72%表达SCF，共表达率为68%。在HONE-1 NPC细胞中证实了c-kit和SCF与p145（c-kit）酪氨酸自磷酸化的共表达。此外，c-kit的表达水平及其自磷酸化状态不受爱泼斯坦-巴尔核抗原1（EBNA1）和潜伏膜蛋白1（LMP1）瞬时共表达的明显影响。因此，c-kit和SCF的共表达常见于鼻咽上皮和NPC中，且在HONE-1 NPC细胞中存在自激活，可能独立于EBNA1和LMP1的共表达。所有这些发现表明，SCF/c-kit信号的自激活可能是鼻咽上皮屏障和鼻咽黏膜表面免疫功能的有效调节因子，可能有助于NPC的发生和进展。需要进一步的分子分析来评估在NPC中使用酪氨酸激酶抑制剂进行治疗的可能性，类似于用STI571治疗胃肠道间质瘤。
