3 research outputs found
Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma
Gliomas are the most common intracranial primary tumors, for which very few therapeutic options are available. The most malignant subtype is the glioblastoma, a disease associated with a 5-year survival rate lower than 5%. Given that research in glycobiology continues highlighting the role of glycans in tumor cell biology, it offers an interesting niche for the search of new therapeutic targets. In this study, we characterized aberrant glycosylation and its impact on cell biology over a broad panel of high- and low-grade glioma cell lines. Results show high expression of terminal Lewis glycans, mainly SLex, and overexpression of sialyl- and fucosyltransferases involved in their biosynthesis in high-grade glioma cell lines. Moreover, we report an association of complex multi-antennary N-glycans presenting β1,6-GlcNAc branches with the high-grade glioma cells, which also overexpressed the gene responsible for these assemblies, MGAT5. In addition, downmodulation of N-glycosylation by treatment with the inhibitors Tunicamycin/Swainsonine or MGAT5 silencing decreased SLex expression, adhesion and migration in high-grade glioma cells. In contrast, no significant changes in these cell capacities were observed in low-grade glioma after treatment with the N-glycosylation inhibitors. Furthermore, inhibition of histone deacetylases by Trichostatin A provoked an increase in the expression of SLex and its biosynthetic related glycosyltransferases in low-grade glioma cells. Our results describe that aggressive glioma cells show high expression of Lewis glycans anchored to complex multi-antennary N-glycans. This glycophenotype plays a key role in malignant cell behavior and is regulated by histone acetylation dependent mechanisms.Fil: Cuello, HĂ©ctor Adrián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Ferreira, Gretel MagalĂ. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes; ArgentinaFil: Gomez Toledo, Alejandro. Lund University; SueciaFil: Segatori, Valeria InĂ©s. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad Nacional de Quilmes; Argentin
Mimicry of Tumour-Associated Carbohydrates: Is It a Promising Option for Cancer Treatment?
Modulation of the immune system has been demonstrated as a powerful approach to treating cancer. Immunotherapies are generally classified as active or passive according to their ability to trigger the immune system. During the last decades, information regarding the relevance of aberrant glycosylation as a major player in tumour biology encouraged expectations for the development of new therapeutic strategies directed at glycans. Several tumour-associated carbohydrate antigens (TACAs) have been identified and validated as suitable immunotherapeutic targets, leading to promising therapeutic developments. It is known that TACAs are poorly immunogenic since they are unable to trigger a proper immune response. Given that they are not presented by major histocompatibility complex (MHC) molecules and that they induce immune tolerance, the development of active immunotherapeutic strategies against TACAs is a real challenge. However, antitumor strategies based on mimetics of TACAs have been developed and show promising results. Active immunotherapies based on TACAs mimicry can currently be grouped into strategies based on the use of mimetic peptides and anti-idiotype (Id) antibodies. In this review, we discussed the scientific basis on which these strategies are based and the available therapeutic options that have shown the best results in preclinical studies and in clinical practice
Mimicry of Tumour-Associated Carbohydrates: Is It a Promising Option for Cancer Treatment?
Modulation of the immune system has been demonstrated as a powerful approach to treating cancer. Immunotherapies are generally classified as active or passive according to their ability to trigger the immune system. During the last decades, information regarding the relevance of aberrant glycosylation as a major player in tumour biology encouraged expectations for the development of new therapeutic strategies directed at glycans. Several tumour-associated carbohydrate antigens (TACAs) have been identified and validated as suitable immunotherapeutic targets, leading to promising therapeutic developments. It is known that TACAs are poorly immunogenic since they are unable to trigger a proper immune response. Given that they are not presented by major histocompatibility complex (MHC) molecules and that they induce immune tolerance, the development of active immunotherapeutic strategies against TACAs is a real challenge. However, antitumor strategies based on mimetics of TACAs have been developed and show promising results. Active immunotherapies based on TACAs mimicry can currently be grouped into strategies based on the use of mimetic peptides and anti-idiotype (Id) antibodies. In this review, we discussed the scientific basis on which these strategies are based and the available therapeutic options that have shown the best results in preclinical studies and in clinical practice.Fil: Segatori, Valeria InĂ©s. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de OncologĂa Molecular; ArgentinaFil: Ferreira, Gretel MagalĂ. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de OncologĂa Molecular; ArgentinaFil: Rojo, Selene. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de OncologĂa Molecular; ArgentinaFil: Nogueira, Aylen Camila. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de OncologĂa Molecular; ArgentinaFil: Castillo, Jeremias Omar. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de OncologĂa Molecular; ArgentinaFil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de OncologĂa Molecular; ArgentinaFil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de OncologĂa Molecular; Argentin