Relevance of Thymic Stromal Lymphopoietin on the Pathogenesis of Glioblastoma: Role of the Neutrophil.
Autor: | Infante Cruz A; Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina., Coronel JV; Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina., Saibene Vélez P; Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.; Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina., Remes Lenicov F; Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires - CONICET, Paraguay 2155, Buenos Aires, Argentina., Iturrizaga J; División Neurocirugía, Instituto de Investigaciones Médicas A Lanari, Universidad de Buenos Aires, Av. Combatientes de Malvinas 3150, Buenos Aires, Argentina., Abelleyro M; Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina., Rosato M; Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.; Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina., Shiromizu CM; Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina., Candolfi M; Instituto de Investigaciones Biomédicas (INBIOMED UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina., Vermeulen M; Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina., Jancic C; Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.; Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina., Yasuda E; Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina., Berner S; Servicio de Neurocirugía de la Clínica y Maternidad Santa Isabel, Buenos Aires, Argentina., Villaverde MS; Unidad de Transferencia Genética, Área Investigación, Instituto de Oncología Ángel H. Roffo, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina., Salamone GV; Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina. salamone.gabriela@gmail.com.; Departamento de Microbiología, Parasitología e Inmunología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. salamone.gabriela@gmail.com. |
---|---|
Jazyk: | angličtina |
Zdroj: | Cellular and molecular neurobiology [Cell Mol Neurobiol] 2024 Apr 01; Vol. 44 (1), pp. 31. Date of Electronic Publication: 2024 Apr 01. |
DOI: | 10.1007/s10571-024-01462-9 |
Abstrakt: | Glioblastoma multiforme (GBM) is the most predominant and malignant primary brain tumor in adults. Thymic stromal lymphopoietin (TSLP), a cytokine primarily generated by activated epithelial cells, has recently garnered attention in cancer research. This study was aimed to elucidate the significance of TSLP in GBM cells and its interplay with the immune system, particularly focused on granulocyte neutrophils. Our results demonstrate that the tumor produces TSLP when stimulated with epidermal growth factor (EGF) in both the U251 cell line and the GBM biopsy (GBM-b). The relevance of the TSLP function was evaluated using a 3D spheroid model. Spheroids exhibited increased diameter, volume, and proliferation. In addition, TSLP promoted the generation of satellites surrounding the main spheroids and inhibited apoptosis in U251 treated with temozolomide (TMZ). Additionally, the co-culture of polymorphonuclear (PMN) cells from healthy donors with the U251 cell line in the presence of TSLP showed a reduction in apoptosis and an increase in IL-8 production. TSLP directly inhibited apoptosis in PMN from GBM patients (PMN-p). Interestingly, the vascular endothelial growth factor (VEGF) production was elevated in PMN-p compared with PMN from healthy donors. Under these conditions, TSLP also increased VEGF production, in PMN from healthy donors. Moreover, TSLP upregulated programed death-ligand 1 (PDL-1) expression in PMN cultured with U251. On the other hand, according to our results, the analysis of RNA-seq datasets from Illumina HiSeq 2000 sequencing platform performed with TIMER2.0 webserver demonstrated that the combination of TSLP with neutrophils decreases the survival of the patient. In conclusion, our results position TSLP as a possible new growth factor in GBM and indicate its modulation of the tumor microenvironment, particularly through its interaction with PMN. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
Externí odkaz: |