Tumor Dormancy Resulting from Subcutaneous Injection to SCID Mice with Cultured Nasopharyngeal Carcinoma Cells Is Mediatedvia IFN-γInduction 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.

Nasopharyngeal carcinoma ecology theory: cancer as multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem

“…For example, Weeraratna AT et al reported that aged lung microenvironment can facilitate a permissive niche and promote the efficient reactivation of dormant melanoma cells in the lung through WNT5A, AXL and MER activators 122 . For the dormancy of NPC, a study from Chinese Taiwan reported the high susceptibility of primary NPC cells following transferred IFN-γgene to the induction of tumor dormancy 123 . Three-dimensional culture studies suggest that the LTBP-2 contribute to tumor cell dormancy in a growth factor favorable microenvironment 124 .…”

The Impact of Mesenchymal Stem Cell Source on Proliferation, Differentiation, Immunomodulation and Therapeutic Efficacy

“…Hung et al showed with SCID mice subcutaneously transplanted with human colon cancer cells that intravenously infused MSCs migrated and engrafted to microscopic tumor lesions [87]. By taking advantage of such an unique feature in addition to relatively low immunogenicity, allogeneic MSCs may therefore be used as a novel, universal delivery vehicle of cytokine genes such as IFN-γ or drugs to induce tumor dormancy or other antitumor therapeutic effects [88,89].…”