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Article Dans Une Revue Nature Communications Année : 2020

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

Floriane Pelon
  • Fonction : Auteur
Brigitte Bourachot
  • Fonction : Auteur
Yann Kieffer
  • Fonction : Auteur
Ilaria Magagna
  • Fonction : Auteur
Isabelle Bonnet
  • Fonction : Auteur
Ana Costa
  • Fonction : Auteur
Anne-Marie Givel
  • Fonction : Auteur
Youmna Attieh
  • Fonction : Auteur
Jorge Barbazan
  • Fonction : Auteur
Claire Bonneau
Laetitia Fuhrmann
Danijela Vignjevic
  • Fonction : Auteur
Maria Carla Parrini
  • Fonction : Auteur
Anne Vincent-Salomon
Fatima Mechta-Grigoriou

Résumé

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.
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Dates et versions

hal-03216095 , version 1 (24-01-2020)
hal-03216095 , version 2 (03-05-2021)

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Floriane Pelon, Brigitte Bourachot, Yann Kieffer, Ilaria Magagna, Fanny Mermet-Meillon, et al.. Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-019-14134-w⟩. ⟨hal-03216095v2⟩
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