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Sexual Dimorphism of Cancer-Associated Fibroblasts Governs Matrix and Vascular Organisation in Breast Cancer

Year: 2026
Type: preprint
Abstract: Breast cancer (BC) shows greatest sexual diversity. Increased diagnosis and poorer outcomes in men highlights the need to better understand its biology. We hypothesised that cancer-associated fibroblasts (CAFs), the most abundant cell type in the tumour microenvironment, might define sex-related differences. Using phenotypically matched male and female CAFs generated from breast cancer tissues, we demonstrate distinct transcriptional programmes and functional behaviours associated with extracellular matrix remodelling, cell adhesion, migration and vascular development. Compared to CAFs generated from females BC, those from males generated denser, more complex matrices promoting stronger tumour and endothelial cell adhesion, vascular growth, but less organised capillary network formation. Findings reveal fundamental sex-related variations in CAF phenotype and biology in BC. These findings highlight the need to integrate biological sex into precision oncology to identify opportunities for sex-specific therapeutic strategies in BC.
DOI: 10.64898/2026.08.27.747484
Authors: Peng Liu, Fiona R. Saunders, Matthew Everest, Natthaya Eiamampai, Matthew P. Humphries, Camilla Coulson Gilmer, Giulia Conti, Lucy F. Stead, Rasha Abu-Eid, Valerie Speirs
Institutions: University of Aberdeen, Leeds Teaching Hospitals NHS Trust, University of Manchester, Cancer Research UK Manchester Centre, Azienda Ospedaliero-Universitaria Careggi, University of Florence, University of Leeds, University of Birmingham
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: green
Award: G326311722
OpenAlex ID: W7204569742
Cites: 62
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Related to: 10