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Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms.

Abstract：

:Although fibroblast heterogeneity is recognized in primary tumors, both its characterization in and its impact on metastases remain unknown. Here, combining flow cytometry, immunohistochemistry and RNA-sequencing on breast cancer samples, we identify four Cancer-Associated Fibroblast (CAF) subpopulations in metastatic lymph nodes (LN). Two myofibroblastic subsets, CAF-S1 and CAF-S4, accumulate in LN and correlate with cancer cell invasion. By developing functional assays on primary cultures, we demonstrate that these subsets promote metastasis through distinct functions. While CAF-S1 stimulate cancer cell migration and initiate an epithelial-to-mesenchymal transition through CXCL12 and TGFβ pathways, highly contractile CAF-S4 induce cancer cell invasion in 3-dimensions via NOTCH signaling. Patients with high levels of CAFs, particularly CAF-S4, in LN at diagnosis are prone to develop late distant metastases. Our findings suggest that CAF subset accumulation in LN is a prognostic marker, suggesting that CAF subsets could be examined in axillary LN at diagnosis.

journal_name

Nat Commun

journal_title

Nature communications

authors

Pelon F,Bourachot B,Kieffer Y,Magagna I,Mermet-Meillon F,Bonnet I,Costa A,Givel AM,Attieh Y,Barbazan J,Bonneau C,Fuhrmann L,Descroix S,Vignjevic D,Silberzan P,Parrini MC,Vincent-Salomon A,Mechta-Grigoriou F

doi

10.1038/s41467-019-14134-w

subject

Has Abstract

pub_date

2020-01-21 00:00:00

pages

404

issue

1

issn

2041-1723

pii

10.1038/s41467-019-14134-w

journal_volume

11

pub_type

杂志文章

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