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. We used 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 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) was the most upregulated gene in metastatic LN LECs, and its expression on LECs was TGF-b 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.
import lamindb as ln
import spatialdata as sd
coll = ln.Collection.get(key="geo-gse298872")
coll.ordered_artifacts.df() # the 4 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]
# …or load each straight into memory as a SpatialData object:
sdatas = {a.key: sd.read_zarr(a.cache()) for a in coll.ordered_artifacts.all()}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<sup>+</sup> subcapsular sinus LECs, while inducing an increase in capillary-like CD200<sup>+</sup> HEY1<sup>+</sup> 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.
Visium HD 
Visium HD 
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Visium HD @article{Eichin_2025,
title = {Breast cancer remodels lymphatics in sentinel lymph nodes},
volume = {16},
ISSN = {2041-1723},
url = {http://dx.doi.org/10.1038/s41467-025-64981-z},
DOI = {10.1038/s41467-025-64981-z},
number = {1},
journal = {Nature Communications},
publisher = {Springer Science and Business Media LLC},
author = {Eichin, Dominik and Lehotina, Diana and Kauko, Anni and Uenaka, Maki and Leppänen, Meri and Elima, Kati and Piipponen, Minna and Lönnberg, Tapio and Boström, Pia and Koskivuo, Ilkka and Aittokallio, Tero and Hollmén, Maija and Takeda, Akira and Jalkanen, Sirpa},
year = {2025},
month = Nov
}