Dataset Information

Aging promotes a RAGE-dependent increase in breast cancer metastasis

ABSTRACT: Breast cancer incidence and mortality increase with age, but the mechanisms linking aging to metastasis remain unclear. Most preclinical studies use young animal models, limiting insight into how the aged microenvironment influences cancer. Here, we show that aging markedly increases breast cancer metastasis in multiple mouse models, and this effect is dependent on host expression of the Receptor for Advanced Glycation End-products (RAGE). Aging increased tumor RAGE ligand levels, including S100A8/9 and AGEs, and induced RAGE-dependent changes in inflammatory, EMT, angiogenic, and extracellular matrix gene programs in tumors. Circulating cytokines and S100A8/9 from aged hosts promoted tumor cell invasion, which was suppressed by RAGE or S100A8/9 inhibition. In human breast cancers, elevated AGER expression and enrichment of aging- and RAGE-associated transcriptional signatures correlated with poorer survival, especially in older patients. These findings identify RAGE as a mechanistic link between aging and metastasis and a potential therapeutic target in older patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE321656 | GEO | 2026/03/23

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Burgeoning evidence highlights seminal roles for microglia in the pathogenesis of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). The receptor for advanced glycation end products (RAGE) binds ligands relevant to ALS that accumulate in the diseased spinal cord and RAGE has been previously implicated in the progression of ALS pathology. We generated a novel mouse model to temporally delete Ager from microglia in the murine SOD1G93A model of ALS. Microglia Ager deficient SOD1G93A mice and controls were examined for changes in survival, motor function, gliosis, motor neuron numbers, and transcriptomic analyses of lumbar spinal cord. Furthermore, we examined bulk-RNA-sequencing transcriptomic analyses of human ALS cervical spinal cord. Transcriptomic analysis of human cervical spinal cord reveals a range of AGER expression in ALS patients, which was negatively correlated with age at disease onset and death or tracheostomy. The degree of AGER expression related to differential expression of pathways involved in extracellular matrix, lipid metabolism, and intercellular communication. Microglia display increased RAGE immunoreactivity in the spinal cords of high AGER expressing patients and in the SOD1G93A murine model of ALS vs. respective controls. We demonstrate that microglia Ager deletion at the age of symptomatic onset, day 90, in SOD1G93A mice extends survival in male but not female mice. Critically, many of the pathways identified in human ALS patients that accompanied increased AGER expression were significantly ameliorated by microglia Ager deletion in male SOD1G93A mice. Our results indicate that microglia RAGE disrupts communications with cell types including astrocytes and neurons, intercellular communication pathways that divert microglia from a homeostatic to an inflammatory and tissue-injurious program. In totality, microglia RAGE contributes to the progression of SOD1G93A murine pathology in male mice and may be relevant in human disease.

Dataset Information

Aging promotes a RAGE-dependent increase in breast cancer metastasis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets