In Vivo Clearance of Apoptotic Debris From Tumor Xenografts Exposed to Chemically Modified Tetrac: Is There a Role for Thyroid Hormone Analogues in Efferocytosis?
Front Endocrinol (Lausanne)
; 13: 745327, 2022.
Article
em En
| MEDLINE
| ID: mdl-35311239
ABSTRACT
Apoptosis is induced in cancer cells and tumor xenografts by the thyroid hormone analogue tetraiodothyroacetic acid (tetrac) or chemically modified forms of tetrac. The effect is initiated at a hormone receptor on the extracellular domain of plasma membrane integrin αvß3. The tumor response to tetrac includes 80% reduction in size of glioblastoma xenograft in two weeks of treatment, with absence of residual apoptotic cancer cell debris; this is consistent with efferocytosis. The molecular basis for efferocytosis linked to tetrac is incompletely understood, but several factors are proposed to play roles. Tetrac-based anticancer agents are pro-apoptotic by multiple intrinsic and extrinsic pathways and differential effects on specific gene expression, e.g., downregulation of the X-linked inhibitor of apoptosis (XIAP) gene and upregulation of pro-apoptotic chemokine gene, CXCL10. Tetrac also enhances transcription of chemokine CXCR4, which is relevant to macrophage function. Tetrac may locally control the conformation of phagocyte plasma membrane integrin αvß3; this is a cell surface recognition system for apoptotic debris that contains phagocytosis signals. How tetrac may facilitate the catabolism of the engulfed apoptotic cell debris requires additional investigation.
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Base de dados:
MEDLINE
Assunto principal:
Integrina alfaVbeta3
/
Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article