Breast cancer remodels lymphatics in sentinel lymph nodes

Dominik Eichin, Diana Lehotina, Anni Kauko, Maki Uenaka, Meri Leppänen, Kati Elima, Minna Piipponen, Tapio Lönnberg, Pia Boström, Ilkka Koskivuo, Tero Aittokallio, Maija Hollmén, Akira Takeda () and Sirpa Jalkanen ()
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Dominik Eichin: University of Turku
Diana Lehotina: University of Turku
Anni Kauko: University of Turku
Maki Uenaka: University of Turku
Meri Leppänen: University of Turku
Kati Elima: University of Turku
Minna Piipponen: University of Turku and Åbo Akademi University
Tapio Lönnberg: University of Turku
Pia Boström: Turku University Hospital
Ilkka Koskivuo: Turku University Hospital
Tero Aittokallio: University of Turku
Maija Hollmén: University of Turku
Akira Takeda: University of Turku
Sirpa Jalkanen: University of Turku

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Cancer metastasis to sentinel lymph nodes (LNs) is often the first marker of potential disease progression. Although it is recognized that tumor-induced lymphangiogenesis facilitates metastasis into LNs in murine models, tumor-induced alterations in human lymphatic vessels remain obscure. Here we use single-cell RNA sequencing and high-resolution spatial transcriptomics to profile lymphatic endothelial cell (LEC) subsets in paired metastatic and non-metastatic LNs obtained from female patients with treatment-naïve breast cancer. Tumor metastasis decreases immunoregulatory LEC subsets, such as PD-L1+ subcapsular sinus LECs, while inducing an increase in capillary-like CD200+ HEY1+ LECs. Matrix Gla protein (MGP) is the most upregulated gene in metastatic LN LECs, and its expression on LECs is TGF-β and VEGF dependent. Upregulated MGP promotes cancer cell adhesion to LN lymphatics. Thus, breast cancer cell metastasis to LNs remodels LEC subsets in human LNs and escalates MGP expression, potentially facilitating cancer cell dissemination through the lymphatic system.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64981-z

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DOI: 10.1038/s41467-025-64981-z

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