Conditioned Medium From Reactive Astrocytes Inhibits Proliferation, Resistance, and Migration of p53-Mutant Glioblastoma Spheroid Through GLI-1 Downregulation

被引：1

作者：

Ribeiro, Jessica Honorato ^{[1
,2
,3
]}

Villarinho, Nicolas Jones ^{[1
,3
,4
]}

Fernandes, Priscila Valverde ^{[5
]}

Spohr, Tania Cristina Leite de Sampaio e ^{[1
,3
,6
]}

Lopes, Giselle Pinto de Faria ^{[3
,7
]}

机构：

[1] Inst Estadual Cerebro Paulo Niemeyer IECPN, Lab Biomed Cerebro, Secretaria Estado Saude, Rio De Janeiro, Brazil

[2] Belgian Nucl Res Ctr, SCK CEN, Radiobiol Unit, Antwerp, Belgium

[3] Univ Fed Rio Janeiro UFRJ, Hosp Univ Clementino Fraga Filho, Programa Pos Grad Anat Patol, Rio De Janeiro, Brazil

[4] Univ Sao Paulo, Inst Biomed Sci ICB, Dept Cell & Dev Biol, Lab Tumor Microenvironm, Sao Paulo, Brazil

[5] Inst Nacl Canc DIPAT INCA, Pathol Div, Dept Pathol, Rio De Janeiro, Brazil

[6] Centogene, Cell Culture & Biobanking, Rostock, Germany

[7] Inst Estudos Mar Almirante Paulo Moreira IEAPM, Nat Prod Div, Dept Marine Biotechnol, Rio De Janeiro, Brazil

来源：

JOURNAL OF CELLULAR BIOCHEMISTRY | 2024年 / 125卷 / 09期

关键词：

conditioned medium; glioblastoma; reactive astrocytes; Sonic hedgehog; spheroids; HEDGEHOG SIGNALING PATHWAY; CELLS; TEMOZOLOMIDE; BETA; PROTEINS; CATENIN; GROWTH; CANCER;

D O I：

10.1002/jcb.30637

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Glioblastoma (GBM) aggressiveness is partly driven by the reactivation of signaling pathways such as Sonic hedgehog (SHH) and the interaction with its microenvironment. SHH pathway activation is one of the phenomena behind the glial transformation in response to tumor growth. The reactivation of the SHH signaling cascade during GBM-astrocyte interaction is highly relevant to understanding the mechanisms used by the tumor to modulate the adjacent stroma. The role of reactive astrocytes considering SHH signaling during GBM progression is investigated using a 3D in vitro model. T98G GBM spheroids displayed significant downregulation of SHH (61.4 +/- 9.3%), GLI-1 (6.5 +/- 3.7%), Ki-67 (33.7 +/- 8.1%), and mutant MTp53 (21.3 +/- 10.6%) compared to the CONTROL group when incubated with conditioned medium of reactive astrocytes (CM-AST). The SHH pathway inhibitor, GANT-61, significantly reduced previous markers (SHH = 43.0 +/- 12.1%; GLI-1 = 9.5 +/- 3.4%; Ki-67 = 31.9 +/- 4.6%; MTp53 = 6.5 +/- 7.5%) compared to the CONTROL, and a synergistic effect could be observed between GANT-61 and CM-AST. The volume (2.0 +/- 0.2 x 107 mu m(3)), cell viability (80.4 +/- 3.2%), and migration (41 +/- 10%) of GBM spheroids were significantly reduced in the presence of GANT-61 and CM-AST when compared to CM-AST after 72 h (volume = 2.3 +/- 0.4 x 107 mu m(3); viability = 92.2 +/- 6.5%; migration = 102.5 +/- 14.6%). Results demonstrated that factors released by reactive astrocytes promoted a neuroprotective effect preventing GBM progression using a 3D in vitro model potentiated by SHH pathway inhibition.

引用

页数：16