Notch1 signaling is activated in cells expressing embryonic stem cell proteins in human primary nasopharyngeal carcinoma.

摘要: Nasopharyngeal carcinoma (NPC), which arises from the mucosal epithelium of nasopharynx, is one most poorly understood and commonly misdiagnosed diseases.1 Although rare in parts world, it common cancers found southern China Southeast Asia, where an annual incidence more than 20 cases per 100,000 reported.1-3 Because NPC occurs anatomic site that accessible to surgeons, high-dose radiotherapy with or without concurrent chemotherapy primary treatment.4,5 The 5-year survival rate about 34 52% has not changed significantly over decades, despite intensive efforts develop effective therapy.4,5 Numerous studies have linked infection Epstein-Barr virus.6 molecular mechanisms underlying carcinogenesis NPC, however, remain unresolved. Studies shown a small subpopulation cells present leukemic humans exhibit marked heterogeneity respect extensive proliferation self-renewal capacity majority tumour cells.7,8 After transplantation into mice severe combined immune deficiency (SCID), these can form tumours phenotypically resemble patient's original tumour.7,8 These are necessary sufficient sustain leukemia therefore tumorigenic. This notion subsequently been verified several solid tumours, including breast,9 brain,10 prostate,11 ovary,12 colon,13 pancreas.14 termed cancer stem (CSCs) because they possess characteristics associated normal cells, specifically ability give rise all cell types particular sample. A recent study showed side population (SP) human line CNE-2, display vitro able vivo.15 However, whether CSCs remains unclear. The findings very important only for our understanding biologic behaviours but also opening new strategies treating cancers. Growing evidence may contribute some individuals' resistance therapy. plausible explanation completely destroyed. Thus, therapeutic target should destroy effectively current treatments while reducing risk relapse metastasis. Consistent this notion, shows SP strong tumorigenic resistant radiotherapy, result recurrence.15 If hypothesis holds true, could be promising therapies. In addition, huge growth CSC field, biological largely unexplored. Notch signaling defines fundamental pathway controlling fate acquisition during embryonic development.16 New many plays diverse roles different malignancies, affects differentiation, proliferation, survival, cell-cycle progression, angiogenesis, possibly self-renewal.17,18 Recent show promotes medulloblastoma “stem cell” survival19 involved initiation pancreatic cancer.20 Notch1 less well understood. In study, 32 patients (1) well-differentiated keratinizing type, (2) moderately differentiated nonkeratinizing (3) undiffer-entiated type according World Health Organization (WHO) classification, were examined by immunocyto-chemistry.21 We (ES) markers SOX2 OCT4 expressed three subtypes NPC. Double immunostaining ES-immuno-reactive coexpressed proliferative markers, suggesting contain stem–like cells. In we Notch1-activated Hes1, downstream signaling, predominantly SOX2- OCT4-positive indicating activation Our suggest signaling–mediated might role tumorigenesis progression humans.