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

Floriane Pelon, Brigitte Bourachot, Yann Kieffer, Ilaria Magagna, Fanny Mermet-Meillon, Isabelle Bonnet, Ana Costa, Anne-Marie Givel, Youmna Attieh, Jorge Barbazan, Claire Bonneau, Laetitia Fuhrmann, Stéphanie Descroix, Danijela Vignjevic, Pascal Silberzan, Maria Carla Parrini, Anne Vincent-Salomon and Fatima Mechta-Grigoriou ()
Additional contact information
Floriane Pelon: PSL Research University
Brigitte Bourachot: PSL Research University
Yann Kieffer: PSL Research University
Ilaria Magagna: PSL Research University
Fanny Mermet-Meillon: PSL Research University
Isabelle Bonnet: PSL Research University, Sorbonne Université
Ana Costa: PSL Research University
Anne-Marie Givel: PSL Research University
Youmna Attieh: PSL Research University
Jorge Barbazan: PSL Research University
Claire Bonneau: PSL Research University
Laetitia Fuhrmann: Institut Curie Hospital
Stéphanie Descroix: Institut Pierre-Gilles de Gennes, CNRS UMR168
Danijela Vignjevic: PSL Research University
Pascal Silberzan: PSL Research University, Sorbonne Université
Maria Carla Parrini: PSL Research University
Anne Vincent-Salomon: Institut Curie Hospital
Fatima Mechta-Grigoriou: PSL Research University

Nature Communications, 2020, vol. 11, issue 1, 1-20

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-14134-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14134-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-14134-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().