Abstract
BackgroundTumours are not only composed of malignant cells but also consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour. Because the ageing process induces accumulation of senescent cells in the body, this micro-environment is thought to be different in cancers occurring in old patients compared with younger patients. More specifically, senescence-related fibroblastic features, such as the senescence-associated secretory profile (SASP) and the induction of autophagy, are suspected to stimulate tumour growth and progression.MethodsWe compared gene expression profiles in stromal fields of breast carcinomas by performing laser capture microdissection of the cancer-associated stroma from eight old (aged ≥80 years at diagnosis) and nine young (aged <45 years at diagnosis) patients with triple-negative breast cancer. Gene expression data were obtained by microarray analysis (Affymetrix). Differential gene expression and gene set enrichment analysis (GSEA) were performed.ResultsDifferential gene expression analysis showed changes reminiscent of increased growth, de-differentiation and migration in stromal samples of older versus younger patients. GSEA confirmed the presence of a SASP, as well as the presence of autophagy in the stroma of older patients.ConclusionsWe provide the first evidence in humans that older age at diagnosis is associated with a different stromal micro-environment in breast cancers. The SASP and the presence of autophagy appear to be important age-induced stromal features.
Highlights
Tumours are composed of malignant cells and consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour
Extreme age categories were chosen to maximise the probability of detecting significant age-related differences
We looked at the individual gene expression results for these genes, but we compiled them using a gene set enrichment strategy that reflects the representation of these genes among the top up- or down-regulated genes in old and young stromal samples
Summary
Tumours are composed of malignant cells and consist of a stromal micro-environment, which has been shown to influence cancer cell behaviour. Because the ageing process induces accumulation of senescent cells in the body, this micro-environment is thought to be different in cancers occurring in old patients compared with younger patients. Tumoural masses are not exclusively composed of malignant cells; they comprise a stromal component containing endothelial cells, (myo)fibroblasts, smooth. Brouwers et al Breast Cancer Research (2017) 19:78 environment with stimulation of proliferation, migration/invasion and de-differentiation. The incidence of breast cancer, the most frequent tumour occurring in women, increases with age [15, 16]. Cancer in older patients is thought to arise from lifelong exposure to harmful stimuli, such as DNA-damaging agents, oxidative stress factors and telomeric loss. Breast cancer in young patients usually reflects either a genetic defect or the impact of early life-transforming effects on an immature breast epithelium
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