Language

English

Publication Date

7-28-2026

Journal

Cancer Letters

DOI

10.1016/j.canlet.2026.218538

PMID

42036011

PMCID

PMC13137461

PubMedCentral® Posted Date

5-5-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Notch signaling is an emerging regulator of liposarcoma (LPS), but its role in mediating communication with the tumor microenvironment (TME) is unclear. Here, we investigate how Notch activation (NICD overexpression) alters the proteomes of LPS-derived extracellular vesicles (EVs). We used quantitative mass spectrometry to profile the EV proteome in multiple contexts: cultured LPS cells, LPS tumor, circulating EVs of LPS-bearing mice, and human LPS samples. We found that Notch signaling increases the secretion of EV proteins that favor tumor progression and metastasis but suppresses immune responses in murine LPS cells. Overlapping murine and human LPS data identifies 18 proteins that are increased in LPS EVs of both species, including endotrophin as a biomarker of LPS. Functional analysis supports a role of LPS EVs in regulating gene expression and behaviors of endothelial cells in TME. Together, these data demonstrate that in addition to its known function in driving tumorigenesis, Notch signaling also regulates TME through EV secretion.

Keywords

Animals, Humans, Extracellular Vesicles, Signal Transduction, Liposarcoma, Tumor Microenvironment, Cell Line, Tumor, Mice, Receptors, Notch, Gene Expression Regulation, Neoplastic

Published Open-Access

yes

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