Dataset Information

Breast cancer remodels lymphatics in sentinel lymph nodes

ABSTRACT: Cancer metastasis into sentinel lymph nodes (LNs) is a crucial determinant of patient mortality. While it is recognized that tumor-induced lymphangiogenesis facilitates metastasis into LNs in murine models, the tumor-induced alterations in human lymphatic vessels remain obscure. Here we utilized single-cell RNA-seq to profile lymphatic endothelial cell (LEC) subsets in paired metastatic and non-metastatic LNs obtained from breast cancer patients. Tumor metastasis leads to a decrease in inflammatory LEC subsets such as subcapsular sinus LECs, while inducing increase of immunosuppressive CD200+ LECs. Matrix Gla protein (MGP) was the most upregulated gene in metastatic LN LECs, and its expression on LECs was VEGF and TGF-b dependent. Silencing MGP in LECs revealed that MGP promotes cancer cell adhesion to LECs. Thus, breast cancer cell metastasis into LNs remodels LEC subsets in human LNs and escalates MGP expression, which potentially facilitates the dissemination of cancer cells through lymphatics.

ORGANISM(S): Homo sapiens

PROVIDER: GSE248214 | GEO | 2025/09/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Invasion of lymphatic vessels is a key step in the metastasis of primary tumour cells to draining lymph nodes. Recent evidence indicates that such metastasis can be facilitated by tumour lymphangiogenesis, although it remains unclear whether this is a consequence of increased lymphatic vessel numbers or alteration in the properties of the vessels themselves. Here we have addressed this important question by comparing the RNA profile of normal dermal lymphatic endothelial cells (LEC) with those isolated from tumours of murine T-241/VEGF-C metastatic fibrosarcoma. Our findings reveal significant changes in the expression of some 792 genes in tumour lymphatics (â?¥ 2 fold up/downregulation, p â?¤ 0.05), involving particularly transcripts associated with junctional adhesion, immunomodulation, extracellular matrix and vessel growth/patterning, several of which we have confirmed by RT-PCR and/or immunohistochemistry. Interestingly, this altered phenotype could not be attributed solely to VEGF-C induced lymphoproliferation, as no similar change in gene expression was reported when human LEC were cultured with VEGF-C in vitro. Moreover, we show that a key protein upregulated in the mouse model, namely the tight junction protein Endothelial Cell Specific Adhesion Molecule (ESAM), is similarly upregulated in tumour lymphatic vessels from 2/2 patients with head and neck squamous cell carcinoma and 4/4 patients with aggressive bladder carcinoma. These findings demonstrate a previously unrecognized influence of tumour environment on lymphatic gene expression and identify candidate tumour specific vessel markers that may prove valuable for either prognosis or therapy. Experiment Overall Design: Here we have investigated the invasion of lymphatic vessels as a key step in the metastasis of primary tumour cells to draining lymph nodes by comparing the gene expression profile of normal dermal lymphatic endothelial cells (LEC) with those isolated from tumours of murine T241/VEGF-C/GFP metastatic fibrosarcoma. Three biological replicates were analyzed from each group.

Dataset Information

Breast cancer remodels lymphatics in sentinel lymph nodes

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets