Sexual Dimorphism of Cancer-Associated Fibroblasts Governs Matrix and Vascular Organisation in Breast Cancer
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,…
Breast cancer (BC) demonstrates significant sexual disparities, with men experiencing higher diagnosis rates and worse prognoses, emphasizing the need for a deeper understanding of its underlying biology. The researchers hypothesized that cancer-associated fibroblasts (CAFs)—the most prevalent cell type in the tumour microenvironment—could be responsible for these sex-related differences.
By generating phenotypically matched male and female CAFs from breast cancer tissues, they uncovered distinct transcriptional programs and functional behaviors linked to extracellular matrix remodelling, cell adhesion, migration, and vascular development. Notably, CAFs derived from males from breast cancer patients generated denser and more complex matrices, which fostered stronger adhesion between tumour and endothelial cells, accelerated vascular growth, yet resulted in less organized capillary network formation compared to those from females.
These findings underscore the importance of integrating biological sex into precision oncology, potentially unveiling opportunities for sex-specific therapeutic strategies in BC.
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