Soluble ICAM-1 a Pivotal Communicator between Tumors and Macrophages, Promotes Mesenchymal Shift of Glioblastoma.
Adv Sci (Weinh)
; 9(2): e2102768, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34813169
ABSTRACT
Despite aggressive clinical treatment, recurrence of glioblastoma multiforme (GBM) is unavoidable, and the clinical outcome is still poor. A convincing explanation is the phenotypic transition of GBM cells upon aggressive treatment such as radiotherapy. However, the microenvironmental factors contributing to GBM recurrence after treatment remain unexplored. Here, it is shown that radiation-treated GBM cells produce soluble intercellular adhesion molecule-1 (sICAM-1) which stimulates the infiltration of macrophages, consequently enriching the tumor microenvironment with inflammatory macrophages. Acting as a paracrine factor, tumor-derived sICAM-1 induces macrophages to secrete wingless-type MMTV integration site family, member 3A (WNT3A), which promotes a mesenchymal shift of GBM cells. In addition, blockade of either sICAM-1 or WNT3A diminishes the harmful effect of radiation on tumor progression. Collectively, the findings indicate that cellular crosstalk between GBM and macrophage through sICAM-1-WNT3A oncogenic route is involved in the mesenchymal shift of GBM cells after radiation, and suggest that radiotherapy combined with sICAM-1 targeted inhibition would improve the clinical outcome of GBM patients.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Glioblastoma
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Molécula 1 de Adesão Intercelular
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Macrófagos
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Mesoderma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article