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The footprint of the ageing stroma in older patients with breast cancer

Lookup NU author(s): Dr Olivier Govaere

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2017 The Author(s).Background: Tumours 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. Methods: We 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. Results: Differential 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. Conclusions: We 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.


Publication metadata

Author(s): Brouwers B, Fumagalli D, Brohee S, Hatse S, Govaere O, Floris G, Van den Eynde K, Bareche Y, Schoffski P, Smeets A, Neven P, Lambrechts D, Sotiriou C, Wildiers H

Publication type: Article

Publication status: Published

Journal: Breast Cancer Research

Year: 2017

Volume: 19

Pages: 1-14

Online publication date: 03/07/2017

Acceptance date: 20/06/2017

Date deposited: 07/12/2017

ISSN (print): 1465-5411

ISSN (electronic): 1465-542X

Publisher: BioMed Central Ltd

URL: https://doi.org/10.1186/s13058-017-0871-0

DOI: 10.1186/s13058-017-0871-0


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