RRC ID 85748
Author Ikari A, Ito Y, Taniguchi K, Shibata MA, Kimura K, Iwamoto M, Lee SW.
Title Role of CD44-Positive Extracellular Vesicles Derived from Highly Metastatic Mouse Mammary Carcinoma Cells in Pre-Metastatic Niche Formation.
Journal Int J Mol Sci
Abstract Malignant breast cancers pose a notable challenge when it comes to treatment options. Recently, research has implicated extracellular vesicles (EVs) secreted by cancer cells in the formation of a pre-metastatic niche. Small clumps of CD44-positive breast cancer cells are efficiently transferred through CD44-CD44 protein homophilic interaction. This study aims to examine the function of CD44-positive EVs in pre-metastatic niche formation in vitro and to suggest a more efficacious EV formulation. We used mouse mammary carcinoma cells, BJMC3879 Luc2 (Luc2 cells) as the source of CD44-positive EVs and mouse endothelial cells (UV2 cells) as the recipient cells in the niche. Luc2 cells exhibited an enhanced secretion of EVs expressing CD44 and endothelial growth factors (VEGF-A, -C) under 20% O2 (representative of the early stage of tumorigenesis) compared to its expression under 1% O2 (in solid tumor), indicating that pre-metastatic niche formation occurs in the early stage. Furthermore, UV2 endothelial cells expressing CD44 demonstrated a high level of engulfment of EVs that had been supplemented with hyaluronan, and the proliferation of UV2 cells occurred following the engulfment of EVs. These results suggest that anti-VEGF-A and -C encapsulated, CD44-expressing, and hyaluronan-coated EVs are more effective for tumor metastasis.
Volume 25(17)
Published 2024-9-9
DOI 10.3390/ijms25179742
PII ijms25179742
PMID 39273689
PMC PMC11395953
MeSH Animals Cell Line, Tumor Cell Proliferation Endothelial Cells / metabolism Endothelial Cells / pathology Extracellular Vesicles* / metabolism Female Hyaluronan Receptors* / metabolism Hyaluronic Acid / metabolism Mammary Neoplasms, Animal / metabolism Mammary Neoplasms, Animal / pathology Mice Neoplasm Metastasis Tumor Microenvironment Vascular Endothelial Growth Factor A / metabolism
IF 4.556
Resource
Human and Animal Cells UV♀2(RCB1994)