Necroptotic astrocytes contribute to maintaining stemness of disseminated medulloblastoma through CCL2 secretion.

ABSTRACT:

Background

Medulloblastoma (MB) with metastases at diagnosis and recurrence correlates with poor prognosis. Unfortunately, the molecular mechanism underlying metastases growth has received less attention than primary therapy-naïve MB. Though astrocytes have been frequently detected in brain tumors, their roles in regulating the stemness properties of MB stem-like cells (MBSCs) in disseminated lesions remain elusive.

Methods

Effects of tumor-associated astrocyte (TAA)-secreted chemokine C-C ligand 2 (CCL2) on MBSC self-renewal was determined by immunostaining analysis. Necroptosis of TAA was examined by measuring necrosome activity. Alterations in Notch signaling were examined after inhibition of CCL2. Progression of MBSC-derived tumors was evaluated after pharmaceutical bloc

SUBMITTER: Liu H 

PROVIDER: S-EPMC7229261 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature