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Fibroblast heterogeneity drives metastatic spread in breast cancer through distinct mechanisms

The major cause of death among breast cancer patients is metastatic dissemination, suggesting that understanding the mechanisms driving this process remains an unmet medical need. Here, by concomitantly using 5 markers, we identify 4 Carcinoma-Associated Fibroblasts (CAF) subsets in primary tumors and corresponding metastatic lymph nodes (LN). Two CAF subsets, called CAF-S1 and CAF-S4, correlate with the proportion of cancer cells in invaded LN and exert distinct functions in tumor cell spread. CAF-S1 promote cancer cell migration and initiates an epithelial to mesenchymal transition through a CXCL12 / TGFb positive loop. For their part, the highly contractile CAF-S4 foster cancer cell motility and invasion in 3-dimensional matrix via Notch pathway activation. Finally, CAF-S1 and CAF-S4 accumulation in LN is a new prognostic factor at diagnostic, independent of breast cancer subtypes and LN status, strengthening the validity of our findings in human breast cancer pathophysiology.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001005744 Illumina HiSeq 2500 28
Publications Citations
Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms.
Nat Commun 11: 2020 404
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