Rapid tumor recurrence in a novel murine GBM surgical model is associated with Akt/PD-L1/vimentin signaling.
Biochem Biophys Res Commun
; 569: 1-9, 2021 09 10.
Article
en En
| MEDLINE
| ID: mdl-34216991
ABSTRACT
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor without curable therapy. Surgical resection remains the first choice of patients with GBM but tumors relapse rapidly even combined with conventional chemoradiotherapy. The mechanism of GBM rapid recurrence is poorly understood, which is largely due to the lack of an appropriate animal model, thus heavily impedes the improvement of postoperative therapy. Here we established a highly reproducible mouse GBM surgical model by using the syngeneic G422TN-GBM cells, which faithfully recapitulates the features of rapid recurrence of human GBM after surgery. Implanting 2 × 103-5 × 104 of G422TN-GBM cells in mouse cerebral cortex caused death in all animal within 23 days, while surgery was an effective therapy but not curable. After complete removal of visible tumors on day 5-9 of tumor growth, the tumors recurred macroscopically within 5 days accompanied by increasing infiltrative cancer foci. Mechanistically, the rapid recurrence of resected tumors was positively correlated to early Akt activation, which subsequently upregulated PD-L1/Vimentin and promoted proliferation/migration of cancer cells. In addition, environmental astrocytic activation with strong PD-L1 signal was prominent. Taken together, we provided a novel GBM surgical recurrence model for preclinical studies and suggested complicated recurring mechanisms involving in strong oncogenic signaling as well as immune inhibitory signals from both GBM cells and their neighboring astrocytes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Vimentina
/
Neoplasias Encefálicas
/
Transducción de Señal
/
Glioblastoma
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Proteínas Proto-Oncogénicas c-akt
/
Antígeno B7-H1
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
China