Dataset Information

Mapping the niche of breast cancer metastases in lung and liver [scRNA-seq-10x-o26674]

ABSTRACT: Breast cancer progression to visceral organs such as lung and liver is regarded as a dreadful event, unequivocally associated with a poor prognosis. Yet, these vital sites are characterized by highly diverse cellular microenvironments and physiological functions, suggesting that they may influence cancer cells behavior in divergent ways. Unexpectedly, we find that while the liver microenvironment fosters metastasis-boosting properties of its metastatic seeds and favors secondary spread, the lungs impose a drastic roadblock to the same processes. Using patient data and mouse models of triple negative breast cancer (TNBC) that spontaneously metastasize to visceral organs, coupled with genetic barcode-mediated metastasis tracing, niche labeling technology and single cell analysis of both tumor cells and their direct microenvironment at each site, we characterize this dichotomy and identify differential microenvironmental factors that contribute to liver vs lung metastasis biology. Mechanistically, we uncover pulmonary cytokines, such as Granulin, whose activity naturally blocks metastatic properties. Conversely, we identify BMP2-producing endothelial cells within the liver metastatic niche, capable to enhance further spread. Together, we reveal an unexpected contrast in the site-specific behavior of visceral metastases in TNBC, highlighting microenvironmental factors that contribute to its geographical diversity, as well as organ-specific opportunities for intervention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288916 | GEO | 2026/09/05

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Introduction: Breast cancer (BC) is the most prevalent malignant disease affecting female patients globally, with triple-negative breast cancer (TNBC) being the subtype linked to the poorest clinical outcome. The liver is a frequent metastatic site of breast cancer. Therefore, elucidating the mechanism underlying liver metastasis in TNBC is crucial for identifying effective diagnostic and therapeutic targets, which holds significant potential for guiding clinical treatment. Objectives: To identify the key gene driving liver metastasis in breast cancer, investigate its mechanism of action, and advance breast cancer treatment. Methods: RNA sequencing was conducted on 4T1-HM3 and its corresponding primary tumor cell 4T1-Pri to identify and screen genes involved in liver metastasis. The enhanced MSLN, a gene encoding mesothelin, was identified in metastatic TNBC cells and tissues using qRT-PCR, Western blotting, and immunohistochemistry. Dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) analysis, and bioinformatics were employed to identify transcription factors regulating MSLN. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), co-immunoprecipitation (co-IP), and immunofluorescence (IF) co-localization were utilized to investigate the mechanism of MSLN action in BC cells. Cellular viability was assessed using a colony formation assay. Cell proliferation and chemosensitivity were assessed using the CCK8 assay. Results: MSLN exhibits aberrantly overexpression in liver-metastatic cells. Elevated MSLN levels are significantly associated with liver metastasis compared to metastases in other organs. MSLN promotes cell proliferation and survival in vitro and TNBC liver metastasis in vivo. Mechanistically, MSLN binds to epidermal growth factor receptor (EGFR) and activates the EGFR-ERK1/2 signaling axis, thereby promoting TNBC cell survival and proliferation during metastasis. Notably, targeting MSLN with a paclitaxel/carboplatin combination can efficiently inhibit liver metastasis of hepatotropic TNBC in a mouse model.

Dataset Information

Mapping the niche of breast cancer metastases in lung and liver [scRNA-seq-10x-o26674]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets