title: Tumor dormancy resulting from subcutaneous injection to SCID mice with cultured nasopharyngeal carcinoma cells is mediated via IFN-γ induction of a highly differentiated phenotype.
abstract: The mechanisms underlying tumor dormancy in human primary lesions and bone marrow metastases of nasopharyngeal carcinoma (NPC) are still not completely understood. The aim of this study was to determine differences in the fates of cultured primary NPC (P-NPC) cells, interferon-γ-transduced primary NPC (IFN-γ-P-NPC) cells, bone marrow metastatic NPC (BM-NPC), and IFN-γ-transduced BM-NPC (IFN-γ-BM-NPC) cells following xenotransplantation into these four groups of SCID mice through subcutaneous injection of 5×10(6) cells/site/animal (4 animals/group). The injected mice were monitored for tumor development at the sites of injection. In only the group injected with IFN-γ-P-NPC cells, the resulting nodules remained small throughout the 60-day observation period after injection, but gradually became palpably prickly. Histopathological examination revealed that these lesions invariably consisted of mostly structures of horny pearls and keratin bridges with occasional apoptotic and degenerative cells. In contrast, animals injected with nontransduced-P-NPC cells developed tumors progressively with occasional central necroses. In the two groups injected with IFN-γ-NPC-BM and NPC-BM cells, progressive growths of tumors were noted, with the latter being at slightly faster rates, whereas the xenografts of both groups showed a poorly differentiated phenotype with abundant vascularity. The study results highlight the high susceptibility of P-NPC but not BM-NPC following IFN-γ gene transfer to the induction of tumor dormancy, which is mediated via induced cell differentiation. Thus, induced cell differentiation could provide a new mechanism by which tumor dormancy is induced.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan .
authors.forename: Andy Shau-Bin
authors.initials: AS
authors.lastname: Chou
authors.forename: Hung-Chang
authors.initials: HC
authors.lastname: Chen
authors.forename: Chia-Rui
authors.initials: CR
authors.lastname: Li
authors.forename: Chin-Hsuan
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Lai-Lei
authors.initials: LL
authors.lastname: Ting
authors.forename: Shuen-Kuei
authors.initials: SK
authors.lastname: Liao
mesh_terms: D000818:Animals; D019046:Bone Marrow Neoplasms / Q000276:immunology / Q000556:secondary; D002277:Carcinoma; D002454:Cell Differentiation / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D053698:Interleukin-6 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D015850:Interleukin-6; D053698:Interleukin-6 Receptor alpha Subunit; D007371:Interferon-gamma