Estrategias terapéuticas para el tratamiento del glioblastoma: papel de la vía de prolactina como blanco terapéutico
Glioblastomas (GB) are the most common and aggressive primary brain tumor in adults. Prolactin (PRL) and its receptor (PRLR) have been associated with the development of hormone-dependent tumors and have been detected in GB biopsies, but their role in gliomagenesis remains unclear. Our aim was to el...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2020
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_6319 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_6319.dir/6319.PDF |
| Aporte de: |
| Sumario: | Glioblastomas (GB) are the most common and aggressive primary brain tumor in adults. Prolactin (PRL) and its receptor (PRLR) have been associated with the development of hormone-dependent tumors and have been detected in GB biopsies, but their role in gliomagenesis remains unclear. Our aim was to elucidate whether this pathway could constitute a therapeutic target in GB. PRL and PRLR were detected in all GB cell lines evaluated. The activation or overexpression of PRLR increased survival and chemo-resistance in GB cells, while PRLR antagonist, ?1?9-G129R-hPRL, led to increased chemo-sensitivity and reduced migration. Meta-analysis of transcriptomic data from glioma biopsies indicated that PRL expression is associated with glioma grade. Stratification by biological sex revealed that male patients with PRL+/PRLRHIGH GB have worse prognostic than those with PRL+/PRLRLOW GB, whereas GII-III male patients exhibited opposite results. We found evidence of sexual dimorphism when we analyzed survival in female patients. Summarizing, PRL pathway favors GB progression and it could hold value as therapeutic target in GB treatment. Comparison of adenoviral vs. baculoviral vectors in vitro and in vivo indicated that the latter may be useful tools for the transfer of PRLR antagonist into the brain to improve the treatment of GB patients. |
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