RESUMO
AIM: Abnormal glycosylation often occurs in tumor cells. T-synthase (core 1 beta 1,3- galactosyltransferase, C1GALT1, or T-synthase) is a key enzyme involved in O-glycosylation. Although T-synthase is known to be important in human tumors, the effects of T-synthase and T-antigen on human tumor responses remain poorly defined. METHODS: In this study, a T-synthase-specific short hairpin RNA (shRNA) or T-synthase-specific eukaryotic expression vector(pcDNA3.1(+)) was transfected into murine Osteosarcoma LM8 cells to assess the effects of T-synthase on T cells and cytokines. RESULTS: The up-regulation of T-synthase promoted the proliferation of osteosarcoma cells in vitro, but it promoted the proliferation of tumor initially up to 2-3 weeks but showed significant growth inhibitory effect after 3 weeks post-implantation in vivo. Osteosarcoma cells with high T-synthase expression in vitro promoted the proliferation and inhibited the apoptosis of CD8+ T cells. Further, T-synthase upregulation promoted CD8+ T-cell proliferation and the increased production of CD4+ T cell-derived IFN-γ cytokines to induce the increased tumor lethality of CTLs. CONCLUSION: Our data suggest that high T-synthase expression inhibits tumor growth by improving the body's anti-tumor immunity. Therefore, using this characteristic to prepare tumor cell vaccines with high immunogenicity provides a new idea for clinical immunotherapy of osteosarcoma.
Assuntos
Linfócitos T CD8-Positivos , Osteossarcoma , Humanos , Animais , Camundongos , Regulação para Cima , Interferon gama/metabolismo , Citocinas , RNA Interferente Pequeno , Osteossarcoma/genética , Osteossarcoma/metabolismo , Proliferação de Células , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Galactosiltransferases/farmacologiaRESUMO
Osteosarcoma ( OS) is the most common primary malignant bone tumor in children and adolescents. Currently, the combination of surgical resection and chemotherapy is the main method of treatment for OS in the clinic.Al-though, the survival rate has been greatly improved in OS patients with localized disease, the 5-year survival rate has re-mained <20%.It is very important to understand the cause of disease, to develop novel drugs or therapeutics, and to learn the disease through animal models.This review will introduce the progress of animal models of osteosarcoma over the last years.
